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Cited by 1Psoriasis: Treatment and PathogenesisDermatology and Skin DiseasesCholesterol and Lipid Metabolism

The DOI matches its Crossref record; 80 of the 82 references it cites were found in a registry or an index; 7 of the 42 sources its claims cite were checked for support.

Macrophage INSIG1 deficiency drives psoriasiform dermatitis via the SREBP2-STAT1 axis

Open access
Li, Xiangzheng, Zang, Yu, Li, Xi, Sheng, Tiancheng, Liu, Shaowen, Chen, Leyi, Xu, Xiaohe, Wang, Lin, Long, Rongzhuo, Zhang, Mengfan, Chen, Xu, Tan, Cheng, Qiang, Lei, He, Yuan·2026·Nature Communications
DOI 10.1038/s41467-026-73278-8PMC PMC13473538
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Abstract

Psoriasis is an autoimmune skin disease, and its pathogenesis remains incompletely understood. As central drivers of psoriasis pathogenesis that bridge innate and adaptive immunity, macrophages are known to be modulated in their function by insulin-induced gene 1 (INSIG1), a regulator of cholesterol synthesis. Bioinformatic analysis of human psoriatic lesions reveals a significant negative correlation between INSIG1 expression and pro-inflammatory cytokine levels (IL-23, IL-17A). Single-cell RNA sequencing (scRNA-seq) and immunofluorescence confirm significantly reduced INSIG1 expression specifically in macrophages from psoriatic skin. In vivo, myeloid-specific Insig1 deficiency exacerbates imiquimod (IMQ)-induced psoriasiform dermatitis, characterized by increased epidermal thickening and immune infiltration. By activating sterol regulatory element-binding protein 2 (SREBP2), INSIG1 deficiency leads to the transcriptional upregulation of STAT1, which drives M1 macrophage polarization and ultimately amplifies psoriatic inflammation. This study reveals an important role of macrophage INSIG1 in regulating inflammatory responses and lipid metabolism, providing insight into the pathogenesis of psoriasis and potential therapeutic targets. Lipid metabolism imbalance strongly associates with psoriasis. The authors here identify macrophage INSIG1 acts independently of cholesterol pathways. Its deficiency activates SREBP2-STAT1, which drives M1 and Th17 responses to exacerbate psoriasiform dermatitis, and complements the metabolism-psoriasis network.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Macrophage INSIG1 is reduced in psoriatic skin and blood, and myeloid-specific Insig1 deletion exacerbates IMQ-induced psoriasiform dermatitis by activating SREBP2, which transcriptionally upregulates STAT1 and drives M1 polarization. The proposed INSIG1–SREBP2–STAT1 axis is largely cholesterol-independent and is suggested as a potential therapeutic target in psoriasis.

Key findings

  • In human data, INSIG1 negatively correlated with psoriasis cytokines in skin bulk RNA-seq (GSE54456, n = 174): IL23A r = −0.5055, IL17A r = −0.5231, and IL12B r = −0.4861. INSIG1 was also reduced in CD14+ monocytes from psoriasis patients (n = 13) versus healthy donors (n = 11) and in CD68+ macrophages from psoriatic lesions (n = 12 per group).
  • Myeloid-specific Insig1 deficiency (Insig1flox/flox; Lyz2-Cre) worsened IMQ-induced psoriasiform dermatitis, with increased scaling, higher PASI scores, increased epidermal thickness, and increased γδ T cells, Th17/Th1 cells, and IL-17A in skin; neutrophil-specific Insig1 deletion (Mrp8-Cre) showed no differences.
  • Mechanistically, INSIG1 deficiency increased STAT1 mRNA, total STAT1, and p-STAT1 without changing the p-STAT1/STAT1 ratio or NF-κB; SREBP2 bound the STAT1 promoter in the −1000 to −1500 bp region, and SREBF2 knockdown or Fatostatin suppressed STAT1 and CD86.
  • INSIG1-deficient macrophages showed increased M1 genes and promoted CD4+ IL-17A+ T cells; their conditioned medium increased HaCaT keratinocyte proliferation, which was attenuated by SREBP2 inhibition. Cholesterol was elevated 1.3-fold in INSIG1-deficient macrophages, but exogenous β-CD-chol mimicking this increase did not alter STAT1.

Methods

  • Human samples included skin paraffin sections from 12 psoriatic patients and 12 healthy controls, PBMCs from 13 psoriasis patients and 11 healthy donors, bulk RNA-seq GSE54456 (n = 174), and scRNA-seq datasets GSE151177 and GSE162183.
  • Mice were female, aged 6–8 weeks; Insig1flox/flox mice were crossed with Lyz2-Cre or Mrp8-Cre. IMQ models received 62.5 mg Aldara cream daily for 6 days; IL-23 models received 500 ng/10 μL intradermally for 11 days; n = 7 mice/group, with PASI scoring.
  • In vitro and mechanistic assays included THP-1 knockdown/overexpression, HEK293T overexpression, BMDMs/peritoneal macrophages, mixed lymphocyte reaction, RNA-seq, lipidomics, luciferase reporter assays, ChIP-seq (GSE129229), EMSA, RT-qPCR, Western blot, flow cytometry, immunofluorescence, ELISA, and crystal violet staining; statistics used t-tests, one-/two-way ANOVA, and Spearman correlation.

Limitations

  • The paper states that scRNA-seq datasets have inherent constraints: GSE151177 may include culture-induced alterations from ex vivo emigrating cell culture, while GSE162183 has a small sample size that may limit statistical power.
  • The paper states that the “cholesterol-independent” conclusion is valid at or below the observed 1.3-fold cholesterol increase; higher cholesterol elevation could still modulate INSIG1–STAT1 interactions, and INSIG1 may regulate other lipid classes.
  • The paper states that it remains unclear whether macrophage INSIG1 modulation is specific to psoriasis or also occurs in other inflammatory skin disorders such as atopic dermatitis; the text also makes evident that LysM-Cre has off-target effects in neutrophils/DCs, and DC-specific in vivo validation was not performed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41467-026-73278-8

Cites

80 of 82 references verified0 citation errors · 2 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

7 of 42 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Elevated cholesterol promotes a pro-inflammatory M1 macrophage phenotype.

    “elevated cholesterol promotes a pro-inflammatory M1 phenotype22–25”
    Quote in the paperSubstantial claim4 of 4 sources checked
    • cites [22] O’Rourke, S. A. et al. Cholesterol crystals drive metabolic reprogramming and M1 macrophage polarisation in primary human macrophages. Atherosclerosis 352, 35–45 (2022). source

      Section 3.1 reports that cholesterol crystals increased M1-associated markers and decreased M2-associated markers in primary human macrophages. The Discussion describes this as polarisation toward a pro-inflammatory M1 phenotype. The source tests cholesterol crystals, however, not elevated cholesterol generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [23] Xu, X., Zhang, A., Li, N., Li, P. L. & Zhang, F. Concentration-dependent diversifcation effects of free cholesterol loading on macrophage viability and polarization. Cell Physiol. Biochem 37, 419–431 (2015). source
    • cites [24] Ramírez, C. M. et al. Crosstalk between LXR and caveolin-1 signaling supports cholesterol efflux and anti-inflammatory pathways in macrophages. Front Endocrinol. (Lausanne) 12, 635923 (2021). source

      The Introduction (page unavailable) says cholesterol accumulation activates LXR and promotes cholesterol efflux, while LXR activation can repress inflammatory genes. The cited paper links cholesterol regulation and inflammation, but the passages found do not say that elevated cholesterol promotes an M1 phenotype. Searches for M1 polarization and cholesterol-induced inflammatory signaling did not establish that claim. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [25] Kim, H. The transcription factor MafB promotes anti-inflammatory M2 polarization and cholesterol efflux in macrophages. Sci. Rep. 7, 7591 (2017). source

      The Introduction links accumulation of cholesterol-rich lipoproteins to inflammation in atherosclerosis and describes M1 macrophages as pro-inflammatory. It does not establish that elevated cholesterol itself promotes M1 polarization; the Discussion treats cholesterol efflux and M2 polarization as separate processes. No page numbers are available in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Findingown data

    INSIG1 deficiency increases M1 macrophage infiltration in skin lesions of Insig1 cKO mice compared with WT mice.

    “FCM and IF analysis revealed that a significant increase was observed in M1 macrophage infiltration in the skin lesions of Insig1 cKO mice compared with the Insig1 WT group”
    Quote in the paperSubstantial claim
  • Findingown data

    INSIG1 expression is negatively correlated with IL23A, IL17A, and IL12B expression in human psoriatic skin.

    “Bioinformatic analysis of human psoriatic lesions reveals a significant negative correlation between INSIG1 expression and pro-inflammatory cytokine levels (IL-23, IL-17A).”
    • Also stated in: § Reduced INSIG1 expression was observed in antigen-presenting cells from psoriatic lesions · plain
      “The results revealed negative correlations of INSIG1 with IL23A (r = −0.5055), IL17A (r = −0.5231), and IL12B (r = −0.4861) expression levels”
    Quote in the paperSubstantial claim
  • Findingown data

    The spleen-to-body weight ratio is significantly increased in Insig1 cKO mice.

    “the spleen-to-body weight ratio, an indirect indicator of systemic inflammation, was significantly increased in Insig1 cKO mice”
    Quote in the paperNot a substantial claim
  • Findingown data

    p-STAT1 and STAT1 MFI in F4/80+ cells are significantly higher in psoriatic skin lesions of Insig1 cKO mice compared to WT mice.

    “FCM and IF analyses of mouse skin tissues showed that the MFI of p-STAT1 and STAT1 in F4/80+ cells were significantly higher in psoriatic skin lesions of Insig1 cKO mice compared to Insig1 WT mice”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim. 26
  • It may state two separate claims as one. 45

  • Probably not a substantial claim.

    Premisecitation

    Cytokines secreted by macrophages, along with their antigen-presenting functions, can promote differentiation and activation of T cells (e.g., Th1 and Th17 cells).

    “The cytokines (e.g., IL-23, IL-6) secreted by macrophages, along with their antigen-presenting functions, can promote the differentiation and activation of T cells (e.g., Th1 and Th17 cells)48–50.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [48] Alshihmani, A. H. H., Mahmoudi, M., Kheder, R. K., Fadaee, A. & Esmaeili, S. A. The M2 macrophages importance role in psoriasis. Immun. Inflamm. Dis. 13, e70211 (2025). source
    • cites [49] Hou, Y. et al. IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis. Protein Cell 9, 1027–1038 (2018). source

      The Introduction says IL-23 is essential for the terminal differentiation of IL-17-producing T effector cells, and the Results show that IL-23-treated macrophages produce cytokines. But the paper does not establish that macrophage-secreted IL-23 or IL-6, together with macrophage antigen presentation, promotes Th1 or Th17 differentiation and activation. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [50] Chen, Y. et al. Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2. Immunity 34, 409–421 (2011). source

      The Introduction says IL-6 and IL-23 provide signals involved in Th17-cell development, and the Discussion describes IL-23 signals as important for later Th17 differentiation. The cited passages do not establish that macrophages secrete those cytokines in this context or that macrophage antigen presentation promotes T-cell activation or Th1 differentiation (no page numbers are available in our copy). (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Findingown data

    Insig1 cKO mice exhibit increased skin scaling, higher PASI scores, and increased epidermal thickness after IMQ treatment compared with Insig1 WT controls.

    “Insig1 cKO mice exhibited increased skin scaling, higher psoriasis area and severity index (PASI) scores, and increased epidermal thickness as assessed by H&E and Ki67 IHC staining”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    STAT1 mRNA is increased in Insig1-deficient primary macrophages and THP-1.shINSIG1 cells.

    “The results confirmed that STAT1 mRNA was increased in these cells”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Insig1 cKO peritoneal macrophages induce higher CD4+ IL-17A+ T cell proportions and elevated IL-23/IL-17A levels compared to Insig1 WT macrophages in MLR.

    “Insig1 cKO pMs induced higher CD4+ IL-17A+ T cell proportions and elevated IL-23/IL-17A levels compared to Insig1 WT macrophages”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    RNA-seq of THP-1.shINSIG1-derived macrophages shows significant upregulation of chemokines (CXCL10, CXCL11, CCL8, CCL2), CD86, and signaling molecules (STAT1, TLR4).

    “The data analysis revealed significant upregulation of multiple genes in INSIG1-knockdown cells, including chemokines (CXCL10, CXCL11, CCL8, and CCL2), the M1 surface costimulatory marker (CD86), and signaling molecules (STAT1, TLR4) critical for inflammatory responses”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    STAT1 and p-STAT1 levels are reduced in HEK293T.GFP-INSIG1 and THP-1.GFP-INSIG1 cells compared to controls, with no notable difference in the p-STAT1/STAT1 ratio.

    “STAT1 and p-STAT1 levels were reduced in HEK293T.GFP-INSIG1 and THP-1.GFP-INISG1 cells compared to control cells, while no notable difference was observed in the p-STAT1/STAT1 ratio”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    INSIG1 deficiency increases total and phosphorylated STAT1 protein abundance but does not alter the p-STAT1/STAT1 ratio, regardless of LPS + IFN-γ treatment.

    “INSIG1 deficiency increased the abundance of both total and phosphorylated STAT1 (p-STAT1), but did not alter the p-STAT1/STAT1 ratio regardless of LPS + IFN-γ treatment”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    NF-κB p65 protein levels and phosphorylation status are not significantly changed in INSIG1-deficient macrophages compared to controls.

    “NF-κB p65, another key transcription factor in M1 macrophage polarization, showed no significant change in protein levels in Insig1-deficient pMs, THP-1.shINSIG1, or HEK293T.GFP-INSIG1 compared to their control cells”
    • Also stated in: § Decreased INSIG1 upregulates STAT1 expression to drive M1 macrophage polarization · plain
      “the phosphorylation status of NF-κB p65 remained comparable between THP-1.shINSIG1 and THP-1.shCON”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    No differences in psoriatic symptoms, epidermal thickness, IL-17A levels, or immune cell infiltration are observed between IMQ-induced neutrophil-specific Insig1 cKOneu and Insig1 WT mice.

    “no differences in psoriatic symptoms, epidermal thickness, IL-17A levels, or immune cell infiltration (Th17 cells and neutrophils) were observed between the IMQ-induced Insig1 cKOneu and Insig1 WT psoriasiform dermatitis mouse models”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    INSIG1 deficiency promotes STAT1 expression and activation, while NF-κB protein levels, phosphorylation status, and nuclear localization remain unchanged.

    “Besides, INSIG1 deficiency promotes STAT1 expression and activation, while NF-κB protein levels, phosphorylation status, and nuclear localization remain unchanged.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: THP-1-derived macrophages are a valid model for human macrophage biology in psoriasis.

  • It may state two separate claims as one.

    Findingown data

    Cytokine profiling of vehicle groups between genotypes revealed detectable but low levels of various cytokines associated with KC proliferation and inflammation, and these levels were markedly elevated in IMQ-treated groups.

    “Cytokine profiling of vehicle groups between genotypes revealed detectable but low levels of various cytokines associated with KC proliferation and inflammation (e.g., Tnf, Il1b, Il6, Il23a, and Cxcl10), and these levels were markedly elevated in the IMQ-treated groups”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    Insig1 deficiency impaired dendritic cell differentiation in vitro, a finding not consistent with the exacerbated inflammatory phenotype observed in vivo.

    “Interestingly, Insig1 deficiency impaired DC differentiation in this setting (Supplementary Fig. 6b, c), a finding that is not consistent with the exacerbated inflammatory phenotype observed in vivo.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Findingown data

    CD11c+ DCs show low INSIG1 expression in healthy skin but variable expression in psoriatic skin, inconsistent with scRNA-seq.

    “CD11c+ DCs showed low INSIG1 expression in healthy skin but variable expression in psoriatic skin, which is inconsistent with the results from scRNA-seq”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    Using several psoriasiform dermatitis mouse models, myeloid-specific INSIG1 deficiency was found to exacerbate disease severity and drive M1 macrophage activation.

    “Using several psoriasiform dermatitis mouse models, myeloid-specific INSIG1 deficiency was found to exacerbate disease severity and drive M1 macrophage activation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IMQ-induced and IL-23-induced mouse models are valid models of psoriasiform dermatitis.

  • It may state two separate claims as one.

    Findingown data

    The proliferation rate of keratinocytes was increased in conditioned medium from THP-1.shINSIG1 cells compared to that from THP-1.shCON cells, and this increase was attenuated by Fatostatin.

    “In line with this, the proliferation rate in KC was increased in the CM from THP-1.shINSIG1 cells compared to that from THP-1.shCON cells, which was attenuated by Fatostatin CM (Fig. 7j, k).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: HaCaT cells are a valid model for studying epidermal biology and psoriatic pathophysiology.

  • It may state two separate claims as one.

    Findingown data

    Mutation of predicted SREBP2 binding sites markedly reduced STAT1 promoter activity, and this activity was further attenuated upon SREBP2 knockdown.

    “Mutation of predicted SREBP2 binding sites, identified through the JASPAR database, markedly reduced STAT1 promoter activity, and this activity was further attenuated upon SREBP2 knockdown (Fig. 6k, l).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    INSIG2 shows low expression with no significant change in M1 and M2 macrophages compared to the HD group.

    “INSIG2 showed a low expression level with no significant change in M1 and M2 macrophages compared to the HD group”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    INSIG1 deficiency-mediated STAT1 activation was suppressed by SREBP2 inhibition with Fatostatin, as was CD86 expression.

    “INSIG1 deficiency-mediated STAT1 activation was suppressed by SREBP2 inhibition with Fatostatin, as was CD86 expression (Fig. 7d–f, Supplementary Fig. 12a).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    scRNA-seq data revealed that INSIG1 is highly expressed in macrophages and demonstrated significant alterations in expression between lesional and non-lesional states.

    “scRNA-seq data revealed that INSIG1 is highly expressed in macrophages and demonstrated significant alterations in expression between lesional and non-lesional states (Fig. 1), which led us to focus subsequent investigations on myeloid-derived immune effector cell function.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Some lipid metabolism-related genes (ABCA1, APOE, ABCC1) were upregulated, whereas others (SCAP, HMGCR, LDLR) remained unaltered in macrophages.

    “Some lipid metabolism-related genes (e.g., ABCA1, APOE, and ABCC1) were upregulated, whereas other genes (e.g., SCAP, HMGCR, LDLR) remained unaltered in macrophages”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Insig1 deficiency leads to increased STAT1 expression in psoriatic lesional macrophages, thereby enhancing their activation.

    “These results indicate that Insig1 deficiency leads to increased STAT1 expression in psoriatic lesional macrophages, thereby enhancing their activation.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Macrophage-specific Insig1 deficiency aggravates IMQ-induced psoriasiform dermatitis, with enhanced KC hyperproliferation and infiltration of γ/δ T, Th1, and Th17 cells.

    “Together, these findings demonstrate that macrophage-specific Insig1 deficiency aggravates IMQ-induced psoriasiform dermatitis, with enhanced KC hyperproliferation and infiltration of γ/δ T, Th1, and Th17 cells.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The IMQ-induced mouse model of psoriasiform dermatitis is a valid model of human psoriasis for studying macrophage INSIG1.

  • It may state two separate claims as one.

    Premisecitation

    Reduced INSIG1 expression activates SREBP2, leading to upregulated expression of inflammatory cytokines in macrophages, such as IL-1β, CXCL10, and CXCL11, independent of the cholesterol synthesis pathway.

    “Moreover, reduced INSIG1 expression activates SREBP2, leading to upregulated expression of inflammatory cytokines in macrophages, such as IL-1β, C-X-C motif chemokine ligand 10 (CXCL10), and CXCL11, independent of the cholesterol synthesis pathway33,34.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Kusnadi, A. et al. The cytokine TNF promotes transcription factor SREBP activity and binding to inflammatory genes to activate macrophages and limit tissue repair. Immunity 51, 241–257.e249 (2019). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [34] Guo, C. et al. Cholesterol homeostatic regulator SCAP-SREBP2 integrates NLRP3 inflammasome activation and cholesterol biosynthetic signaling in macrophages. Immunity 49, 842–856.e847 (2018). source

  • It may state two separate claims as one.

    Interpretationown data

    INSIG1 drives M1 polarization via STAT1, not NF-κB signaling.

    “These findings demonstrate that INSIG1 drives M1 polarization via STAT1, not NF-κB signaling.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IFN-γ primarily activates STAT1, and STAT1 plays a critical role in M1 macrophage polarization.

  • Probably not a substantial claim.

    Premisecitation

    INSIG1 is an endoplasmic reticulum-resident protein that serves as a central regulator of cellular cholesterol and lipid homeostasis by anchoring and inhibiting activation of SREBP transcription factors.

    “INSIG1 is an endoplasmic reticulum-resident protein that serves as a central regulator of cellular cholesterol and lipid homeostasis by anchoring and inhibiting the activation of sterol regulatory element-binding protein (SREBP) transcription factors30.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Yang, T. et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110, 489–500 (2002). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    LXRα antagonizes NF-κB signaling to suppress M1 polarization.

    “LXRα antagonizes nuclear factor kappa-B (NF-κB) signaling to suppress M1 polarization27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Dou, F. et al. Anti-atherosclerotic effects of LXRα agonist through induced conversion of M1 macrophage to M2. Am. J. Transl. Res. 11, 3825–3840 (2019).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    INSIG1 loss activates SREBP2 and upregulates cholesterol biosynthetic genes (e.g., HMGCR, HMGCS1) and increases cholesterol production.

    “Based on reports that INSIG1 loss activates SREBP2 and upregulates cholesterol biosynthetic genes (e.g., HMGCR, HMGCS1) and increases cholesterol production53,54”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [53] Jiang, G. et al. LY86 facilitates ox-LDL-induced lipid accumulation in macrophages by upregulating SREBP2/HMGCR expression. BMC Cardiovasc. Disord. 24, 289 (2024). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [54] Xiao, M. Y. et al. Gypenoside L inhibits hepatocellular carcinoma by targeting the SREBP2-HMGCS1 axis and enhancing immune response. Bioorg. Chem. 150, 107539 (2024). source

  • It may state two separate claims as one.

    Interpretationown data

    INSIG1 deficiency promotes M1 macrophage polarization and T cell-mediated function in psoriasis.

    “Together, these data collectively suggest that INSIG1 deficiency promotes M1 macrophage polarization and T cell–mediated function in psoriasis.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The IMQ-induced mouse model of psoriasiform dermatitis is a valid model of human psoriasis for studying macrophage INSIG1.

  • It may state two separate claims as one.

    Premisecitation

    Psoriasis is characterized by increased frequencies of M1-like monocytes in peripheral blood and enhanced infiltration of M1 macrophages within lesional skin.

    “psoriasis is characterized by increased frequencies of M1-like monocytes in the peripheral blood and enhanced infiltration of M1 macrophages within lesional skin18–21.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [18] Gong, X. & Wang, W. Profiles of innate immune cell infiltration and related core genes in psoriasis. Biomed. Res Int 2021, 6656622 (2021). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [19] Nguyen, C. T. H. et al. Up-regulated expression of CD86 on circulating intermediate monocytes correlated with disease severity in psoriasis. J. Dermatol Sci. 90, 135–143 (2018). source
    • cites [20] Ma, Y. et al. Oroxylin A attenuates psoriasiform skin inflammation by directly targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization. Br. J. Pharm. 181, 5110–5132 (2024). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [21] Sun, Q., Hu, S., Lou, Z. & Gao, J. The macrophage polarization in inflammatory dermatosis and its potential drug candidates. Biomed. Pharmacother. 161, 114469 (2023). source

  • It may state two separate claims as one.

    Interpretationown data

    INSIG1 primarily regulates STAT1 expression rather than STAT1 activation.

    “indicating that INSIG1 primarily regulates STAT1 expression rather than activation”
    • Also stated in: § Decreased INSIG1 upregulates STAT1 expression to drive M1 macrophage polarization · boosted
      “Together, these data support that INSIG1 regulates macrophage polarization primarily by controlling STAT1 expression, rather than affecting STAT1 activation status.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    INSIG1 is essential for STING pathway-mediated antiviral immunity and suppresses NLRP3 inflammasome activation and IL-1β production.

    “INSIG1 is essential for the stimulator of interferon genes (STING) pathway-mediated antiviral immunity and suppresses the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and IL-1β production31,32.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [31] Wang, Q. et al. The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity 41, 919–933 (2014). source
    • cites [32] Xu, T. et al. Ubiquitination of NLRP3 by gp78/Insig-1 restrains NLRP3 inflammasome activation. Cell Death Differ. 29, 1582–1595 (2022). source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    A study reported a negative association between INSIG1 and the pathogenesis of psoriasis.

    “Besides, a study reported a negative association between INSIG1 and the pathogenesis of psoriasis35.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Zhou, X. et al. Single-cell sequencing and machine learning integration to identify candidate biomarkers in psoriasis: INSIG1. J. Inflamm. Res 17, 11485–11503 (2024). source

      Checked before — its earlier verdict is held back until a new check runs.

  • It may state two separate claims as one.

    Premisecitation

    Cholesterol homeostasis is disrupted in psoriatic lesions, with upregulation of cholesterol synthesis pathways, elevated free cholesterol, and disrupted cellular cholesterol homeostasis.

    “spatial proteomic and biochemical analyses demonstrate significant upregulation of cholesterol synthesis pathways, elevated free cholesterol levels, and disrupted cellular cholesterol homeostasis14–17.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [14] Møller, L. B. P. et al. Spatial proteomic profiling reveals increased levels of cholesterol synthesis proteins in psoriasis vulgaris. J. Invest. Dermatol. 145, 3051–3063.e2 (2025). source
    • cites [15] Fortinskaia E. S., et al. [Features of distribution of free and esterified cholesterol in the epidermis, biological membranes and plasma lipoproteins in psoriasis]. Klin. Lab. Diagn., 38-43 (1996).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [16] Mijaljica, D., Townley, J. P., Spada, F. & Harrison, I. P. The heterogeneity and complexity of skin surface lipids in human skin health and disease. Prog. Lipid Res. 93, 101264 (2024). source
    • cites [17] Varshney, P. et al. Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis. Sci. Rep. 6, 19295 (2016). source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    ABCA1 and ABCG1 modulate TLR signaling and efferocytosis, thereby indirectly shaping macrophage activation and inflammatory responses.

    “ABCA1 and ABCG1 modulate toll-like receptor (TLR) signaling and efferocytosis, thereby indirectly shaping macrophage activation and inflammatory responses28,29.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Westerterp, M. et al. Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice. Circ. Res. 112, 1456–1465 (2013). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [29] Yvan-Charvet, L. et al. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions. Circulation 118, 1837–1847 (2008). source

      Checked before — its earlier verdict is held back until a new check runs.

  • It may state two separate claims as one.

    Premisecitation

    INSIG1 deficiency or activation of its downstream signaling promotes increased cellular cholesterol levels.

    “These findings are consistent with previous studies demonstrating that INSIG1 deficiency or activation of its downstream signaling promotes increased cellular cholesterol levels55,56.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [55] Engelking, L. J. et al. Schoenheimer effect explained-feedback regulation of cholesterol synthesis in mice mediated by Insig proteins. J. Clin. Invest. 115, 2489–2498 (2005). source
    • cites [56] Wang, Y. et al. Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages. Cell Rep. 41, 111738 (2022). source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    All animal experiments were performed in accordance with protocols approved by the Animal Welfare and Ethics Committee of China Pharmaceutical University.

    “All animal experiments were performed in accordance with protocols approved by the Animal Welfare and Ethics Committee of China Pharmaceutical University.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    The efficiency of loxP-mediated gene recombination driven by LysM-Cre varies markedly among myeloid cell types, with the highest efficiency in mature macrophages (approximately 83-98%) and much lower efficiency in splenic DCs (about 16%).

    “It is important to note that the efficiency of loxP-mediated gene recombination driven by LysM-Cre varies markedly among myeloid cell types63–65. with the highest efficiency observed in mature macrophages (approximately 83–98%) and much lower efficiency in splenic DCs (about 16%)44.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [63] Shi, J., Hua, L., Harmer, D., Li, P. & Ren, G. Cre driver mice targeting macrophages. Methods Mol. Biol. 1784, 263–275 (2018). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [64] Huang, S. et al. Cre driver efficiency in myeloid lineages across tissues and in a model of myocardial injury. Faseb j. 40, e71497 (2026). source
    • cites [65] Ferro, A. et al. Inhibition of NF-κB signaling in IKKβF/F;LysM Cre mice causes motor deficits but does not alter the pathogenesis of Spinocerebellar ataxia type 1. PLoS ONE 13, e0200013 (2018). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [44] Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R. & Förster, I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8, 265–277 (1999). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    The study protocol was approved by the Ethics Committee of China Pharmaceutical University (Approval No. YSL-202505047).

    “The study protocol was approved by the Ethics Committee of China Pharmaceutical University (Approval No. YSL-202505047).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    The RNA-seq experiment comparing THP-1.shCON and THP-1.shINSIG1 macrophages was independently replicated three times.

    “The experiment was independently replicated three times.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    INSIG1 regulates macrophage polarization primarily by controlling STAT1 expression rather than affecting STAT1 activation status.

    “Together, these data support that INSIG1 regulates macrophage polarization primarily by controlling STAT1 expression, rather than affecting STAT1 activation status.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IFN-γ primarily activates STAT1, and STAT1 plays a critical role in M1 macrophage polarization.

  • It may state two separate claims as one.

    Interpretationown data

    INSIG1 deficiency exacerbates M1 polarization and keratinocyte hyperproliferation by enhancing SREBP2-dependent STAT1 transcription.

    “In summary, these findings demonstrate that INSIG1 deficiency exacerbates M1 polarization and KC hyperproliferation by enhancing SREBP2-dependent STAT1 transcription.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: THP-1-derived macrophages are a valid model for human macrophage biology in psoriasis.
    • Rests on an assumption: HaCaT cells are a valid model for studying epidermal biology and psoriatic pathophysiology.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    CXCL10 can recruit lymphocytes, including Th1 and Th17 cells, to inflammatory sites, thereby amplifying local immune responses.

    “Notably, CXCL10 can recruit lymphocytes, including Th1 and Th17 cells, to inflammatory sites, thereby amplifying local immune responses46,47.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46] Bruchard, M. et al. Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses. Nat. Immunol. 23, 262–274 (2022). source
    • cites [47] Nastase, M. V. et al. Biglycan, a novel trigger of Th1 and Th17 cell recruitment into the kidney. Matrix Biol. 68-69, 293–317 (2018). source

  • It may state two separate claims as one.

    Interpretationown data

    INSIG1 deficiency activates SREBP2, which directly promotes STAT1 transcription.

    “The mechanism underlying this phenomenon was found to involve the activation of SREBP2 by INSIG1 deficiency in macrophages, which directly promotes STAT1 transcription”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IFN-γ primarily activates STAT1, and STAT1 plays a critical role in M1 macrophage polarization.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    WB analyses were performed using 3 independent biological replicates.

    “WB analyses were performed using 3 independent biological replicates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    The clinical study was approved by the Ethics Committee of the Affiliated Hospital of Nanjing University of Chinese Medicine (Approval No. 2022NL-061-02).

    “The Ethics Committee of the Affiliated Hospital of Nanjing University of Chinese Medicine approved this clinical study (Approval No. 2022NL-061-02).”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Aldara vehicle cream contains isostearic acid, which can trigger low-grade innate immune activation, including IL-1 release.

    “It has been reported that Aldara vehicle cream contains isostearic acid, which has been reported to trigger low-grade innate immune activation, including IL-1 release38,39.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38] Walter, A. et al. Aldara activates TLR7-independent immune defense. Nat. Commun. 4, 1560 (2013). source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [39] Wen, H. et al. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12, 408–415 (2011). source

      Checked before — its earlier verdict is held back until a new check runs.

  • It may state two separate claims as one.

    Interpretationown data

    The reduction in STAT1 levels by SREBF2 knockdown was not rescued in double-knockdown macrophages, indicating that SREBP2 is the primary transcriptional factor mediating the transcription of STAT1 downstream of INSIG1.

    “Notably, this reduction was not rescued in double-knockdown macrophages (Fig. 7a–c), indicating that SREBP2 is the primary transcriptional factor mediating the transcription of STAT1 downstream of INSIG1.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Control cell lines were generated using control virus produced by empty vectors (shCON or GFP-CON) and processed in parallel.

    “Control cell lines were generated using control virus produced by empty vectors (shCON or GFP-CON) and processed in parallel.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Band intensities in Western blots were quantified by densitometry using ImageJ and normalized to the corresponding loading control (e.g., GAPDH or β-actin).

    “Band intensities were quantified by densitometry using ImageJ software and normalized to the corresponding loading control (e.g., GAPDH or β-actin).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Cell lines with INSIG1 knockdown or overexpression were validated by RT-qPCR and Western blotting to confirm knockdown efficiency or overexpression levels.

    “Surviving cells were expanded and validated by RT-qPCR and Western blotting to confirm knockdown efficiency or overexpression levels.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationreasoning

    INSIG1 deficiency promotes M1 polarization by upregulating STAT1 transcription and boosting its protein expression.

    “INSIG1 deficiency promotes M1 polarization by upregulating STAT1 transcription and boosting its protein expression.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: THP-1-derived macrophages are a valid model for human macrophage biology in psoriasis.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductnone given

    All animal procedures were performed in compliance with the ARRIVE 2.0 guidelines and the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

    “All animal procedures were performed in compliance with the ARRIVE 2.0 guidelines and the National Institutes of Health Guide for the Care and Use of Laboratory Animals.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    SREBP2-mediated transcriptional upregulation of STAT1 is observable even under LPS + IFN-γ stimulation, indicating that this metabolic regulatory pathway operates in parallel to canonical cytokine-driven STAT1 regulation.

    “Importantly, this SREBP2-mediated transcriptional upregulation was observable even under LPS + IFN-γ stimulation (Supplementary Fig. 8f), indicating that this metabolic regulatory pathway operates in parallel to canonical cytokine-driven STAT1 regulation.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    STAT1 is a direct transcriptional target of SREBP2, showing its binding to and activation of the STAT1 promoter.

    “We demonstrate that STAT1 is a direct transcriptional target of SREBP2, showing its binding to and activation of the STAT1 promoter (Fig. 6j–n).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    The INSIG1-SREBP2-STAT1 axis is a pivotal signaling pathway that promotes macrophage M1 polarization and fuels inflammation in psoriasis.

    “In this study, the INSIG1–SREBP2–STAT1 axis was uncovered as a pivotal signaling pathway that promotes macrophage M1 polarization and fuels inflammation in psoriasis, thereby highlighting its potential as a therapeutic target.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: THP-1-derived macrophages are a valid model for human macrophage biology in psoriasis.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductreasoning

    THP-1.shCON and THP-1.shINSIG1 cell lines were passaged continuously for three generations before lipidomic analysis to ensure stable cellular status and minimize variability from prior culture conditions.

    “Prior to lipidomic analysis, THP-1.shCON and THP-1.shINSIG1 cell lines were passaged continuously for three generations to ensure stable cellular status and to minimize variability associated with prior culture conditions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Informed consent was obtained from all participants.

    “Informed consent was obtained from all participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    The observation of INSIG1 downregulation in macrophages was verified by another scRNA-seq dataset (GSE162183).

    “This observation was also verified by another scRNA-seq dataset (GSE162183)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Three blinded investigators performed the PASI scoring independently.

    “For each mouse on each day, three blinded investigators performed the scoring independently.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    This study establishes macrophage INSIG1 as a pivotal regulator of psoriasis pathogenesis by identifying an INSIG1-SREBP2-STAT1 signaling axis.

    “Taken together, this study establishes macrophage INSIG1 as a pivotal regulator of psoriasis pathogenesis by identifying a INSIG1–SREBP2–STAT1 signaling axis.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    N-SREBP2 binds to the STAT1 promoter and directly promotes STAT1 transcription.

    “Subsequently, N-SREBP2 translocates to the nucleus, where it binds to the STAT1 promoter and directly promotes STAT1 transcription.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    Cell numbers in crystal violet assays were quantified using a standard curve generated by plating defined numbers of cells (1000-40,000 cells per well) and measuring absorbance at 570 nm under identical conditions, with a linear regression model (R2 > 0.99).

    “Cell numbers were quantified using a standard curve generated by plating defined numbers of cells (1000–40,000 cells per well) and measuring absorbance at 570 nm under identical conditions. A linear regression model (R² > 0.99) was used to calculate cell numbers from absorbance values.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Single-cell RNA sequencing data were processed with standard quality control, normalization, and Harmony batch correction.

    “Single-cell RNA sequencing data were processed and analyzed using the Seurat R package (v4.4.0) with standard quality control, normalization, and Harmony batch correction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Differential expression analysis of INSIG1, INSIG2, and lipid metabolism genes was conducted using the Wilcoxon test with Benjamini-Hochberg multiple testing correction.

    “Differential expression analysis of INSIG1, INSIG2, and lipid metabolism genes was conducted using the Wilcoxon test with Benjamini-Hochberg multiple testing correction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductnone given

    RT-qPCR was performed with three technical replicates per sample in each independent experiment, and results from three independent biological replicates were combined for statistical analysis.

    “RT-qPCR was performed with three technical replicates per sample in each independent experiment, and the mean value was used as a single data point. Results from three independent biological replicates were combined for statistical analysis.”
    Quote in the paperNot a substantial claim
65 of 65

  • The paper relies on this without support.

    The IMQ-induced mouse model of psoriasiform dermatitis is a valid model of human psoriasis for studying macrophage INSIG1.

    “To validate this finding, Imiquimod (IMQ)- and IL-23-induced mouse models of psoriasis were established”
    “All these data suggest IMQ- and IL-23-induced mouse models of psoriasis were successfully established.”

  • The paper relies on this without support.

    IFN-γ primarily activates STAT1, and STAT1 plays a critical role in M1 macrophage polarization.

    “Given that IFN-γ primarily activates the transcription factor STAT1, which plays a critical role in M1 macrophage polarization, STAT1 was therefore selected for further investigation.”

  • The paper relies on this without support.

    THP-1-derived macrophages are a valid model for human macrophage biology in psoriasis.

    “To generate THP-1-derived M1-like macrophages, THP-1 cells were treated with phorbol 12-myristate 13-acetate (PMA, 100 nM) (Cat. #524400, Sigma-Aldrich, Germany) for 24 h, followed by Lipopolysaccharides (LPS) (100 ng/mL) (Cat. #L2630, Sigma-Aldrich, Germany) + IFN-γ (20 ng/mL) (Cat. #300-02, Thermo Fisher Scientific Ltd., USA) for another 24 h.”

  • The paper relies on this without support.

    HaCaT cells are a valid model for studying epidermal biology and psoriatic pathophysiology.

    “To model this interaction in vitro, we utilized HaCaT cells, an immortalized human keratinocyte cell line widely used to study epidermal biology and psoriatic pathophysiology.”

  • The paper relies on this without support.

    IMQ-induced and IL-23-induced mouse models are valid models of psoriasiform dermatitis.

    “For the IMQ-induced psoriasiform dermatitis mouse models, after being anesthetized with isoflurane and shaved on the dorsal skin, female C57BL/6 mice (n = 7 /group) received daily topical applications of 62.5 mg Aldara cream (5% imiquimod) on shaved dorsal skin for 6 days.”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting biological replicate counts for Fig. 4e

    Minor

    The Fig. 4 caption assigns four biological replicates to panel e, then states that panels d-n, which include e, have three.

  • INSIG1 is described as both driving and suppressing M1 polarization

    Minor

    The results text says INSIG1 drives M1 polarization via STAT1, whereas the Fig. 4 caption says INSIG1 suppresses it. These statements assign opposite effects to INSIG1.

2 of 2

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Metadata

Authors
Li, X., Zang, Y., Li, X., Sheng, T., Liu, S., Chen, L., Xu, X., Wang, L., Long, R., Zhang, M., Chen, X., Tan, C., Qiang, L., & He, Y.
Affiliations
  • China Pharmaceutical University (CN)
  • University of Macau (MO)
  • Nanjing University of Chinese Medicine (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
  • Tan, Cheng
  • Qiang, Lei
  • He, Yuan
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2026-07-02
Volume
17
Issue
1
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-026-73278-8
PMC
PMC13473538
OpenAlex
W7167010686
Cited by
1
References
82
Citations by year
2026: 1
FWCI
2.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Chongqing Science and Technology Commission (CSTB 2024NSCQ-KJFZZDX0033)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords
psoriasis, INSIG1, macrophages, SREBP2, STAT1, psoriasiform dermatitis, M1 macrophage polarization, Th17 cells, imiquimod-induced dermatitis, lipid metabolism, cholesterol biosynthesis, IL-17A, IL-23, skin inflammation
MeSH terms
Imiquimod, Animals, Dermatitis, Female, Humans, Macrophages, Membrane Proteins, Mice, Inbred C57BL, Psoriasis, Skin, Signal Transduction, Mice, Knockout, Intracellular Signaling Peptides and Proteins, STAT1 Transcription Factor, Mice, Sterol Regulatory Element Binding Protein 2

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