Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity
Open accessAbstract
A defining feature of adaptive immunity is the development of long-lived memory T cells to curtail infection. Recent studies have identified a unique stem-like T-cell subset amongst exhausted CD8-positive T cells in chronic infection1–3, but it remains unclear whether CD4-positive T-cell subsets with similar features exist in chronic inflammatory conditions. Amongst helper T cells, TH17 cells have prominent roles in autoimmunity and tissue inflammation and are characterized by inherent plasticity4–7, although how such plasticity is regulated is poorly understood. Here we demonstrate that TH17 cells in a mouse model of autoimmune disease are functionally and metabolically heterogeneous; they contain a subset with stemness-associated features but lower anabolic metabolism, and a reciprocal subset with higher metabolic activity that supports transdifferentiation into TH1-like cells. These two TH17-cell subsets are defined by selective expression of the transcription factors TCF-1 and T-bet, and by discrete levels of CD27 expression. We also identify signalling via the kinase complex mTORC1 as a central regulator of TH17-cell fate decisions by coordinating metabolic and transcriptional programmes. TH17 cells with disrupted mTORC1 signalling or anabolic metabolism fail to induce autoimmune neuroinflammation or to develop into TH1-like cells, but instead upregulate TCF-1 expression and acquire stemness-associated features. Single-cell RNA sequencing and experimental validation reveal heterogeneity in fate-mapped TH17 cells, and a developmental arrest in the TH1 transdifferentiation trajectory upon loss of mTORC1 activity or metabolic perturbation. Our results establish that the dichotomy of stemness and effector function underlies the heterogeneous TH17 responses and autoimmune pathogenesis, and point to previously unappreciated metabolic control of plasticity in helper T cells. Phenotypically, transcriptionally and metabolically diverse subsets of TH17 cells develop in a chronic autoimmune disease: one subset has inferred stemness features and low anabolic metabolism, while a reciprocal subset has higher metabolic activity that supports transdifferentiation into TH1 cells.
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Mouse non-pathogenic/homeostatic and pathogenic Th17 phenotypes may mirror human Th17 subsets important for immunity against distinct bacteria and fungi.
“the non-pathogenic/homeostatic and pathogenic Th17 cell phenotypes studied in the mouse models may mirror the physiological roles of human Th17 cell subsets that are important for immunity against distinct bacteria and fungi”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [64]
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“Considering that the stemness of T H 17 cells is implicated in the development of autoimmune diseases and it is influenced by lactate ( 45 , 46 ), we wondered whether the lactylation level was associated with the stemness of T H 17 cells.”
Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity
Künzli, M., Schreiner, D., Pereboom, T. C., Swarnalekha, N., Litzler, L. C., Lötscher, J., Ertuna, Y. I., Roux, J., Geier, F. M., Jakob, R. P., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aay5552 · Cited by 113 · see citing works
“mTOR activation was also recently shown to mediate the differentiation of metabolically quiescent, TCF1-positive TH17 cells into inflammatory TH1 effectors (50).”
BackgroundCRISPR screens unveil signal hubs for nutrient licensing of T cell immunity
Long, L., Wei, J., Lim, S. A., Raynor, J. L., Shi, H., Connelly, J. P., Wang, H., Guy, C. S., Xie, B., Chapman, N. M., et al. (2021) · Nature · doi:10.1038/s41586-021-04109-7 · Cited by 111 · see citing works
Self-citationElevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus
Voss, K., Sewell, A. E., Krystofiak, E., Gibson-Corley, K. N., Young, A., Basham, J. H., Sugiura, A., Arner, E. N., Beavers, W. N., Kunkle, D. E., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.abq0178 · Cited by 113 · see citing works
“the conversion of nonpathogenic TH17 cells to proinflammatory pathogenic TH17 cells (61, 62).”
BackgroundHong, H. S., Mbah, N. E., Shan, M., Loesel, K., Lin, L., Sajjakulnukit, P., Correa, L. O., Andren, A. C., Lin, J., Hayashi, A., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abm8182 · Cited by 103 · see citing works
Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications
Fearon, U., Hanlon, M. M., Floudas, A., & Veale, D. J. (2022) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00771-x · Cited by 107 · see citing works
Control of Lymphocyte Fate, Infection, and Tumor Immunity by TCF-1.
Raghu, D., Xue, H.-H., & Mielke, L. (2019) · Trends in immunology · doi:10.1016/j.it.2019.10.006 · Cited by 95 · see citing works
TCF-1: A maverick in T cell development and function
Gounari, F., & Khazaie, K. (2022) · Nature Immunology · doi:10.1038/s41590-022-01194-2 · Cited by 73 · see citing works
Role of TCF‐1 in differentiation, exhaustion, and memory of CD8 + T cells: A review
Zhang, J., Lyu, T., Cao, Y., & Feng, H. (2021) · The FASEB Journal · doi:10.1096/fj.202002566r · Cited by 95 · see citing works
Interactions between neutrophils and T-helper 17 cells
Fan, X., Shu, P., Wang, Y., Ji, N., & Zhang, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1279837 · Cited by 97 · see citing works
“Hypermetabolic Th17 has strong IFN-g expression and supports transdifferentiation to Th1-like cells (50).”
BackgroundNutrients: Signal 4 in T cell immunity
Raynor, J. L., & Chi, H. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221839 · Cited by 94 · see citing works
“Also in EAE, inhibition of glycolysis or mTORC1 activity via Raptor deletion promotes the generation of a TCF-1 + Th17 population with stemness-associated features that fail to induce autoimmunity (Karmaus et al., 2019).”
BackgroundSelf-citationPawlak, M., Ho, A. W., & Kuchroo, V. K. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.09.001 · Cited by 89 · see citing works
SENP7 senses oxidative stress to sustain metabolic fitness and antitumor functions of CD8+ T cells
Wu, Z., Huang, H., Han, Q., Hu, Z., Teng, X.-L., Ding, R., Ye, Y., Yu, X., Zhao, R., Wang, Z., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155224 · Cited by 85 · see citing works
Long-Term Programming of CD8 T Cell Immunity by Perinatal Exposure to Glucocorticoids
Hong, J. Y., Lim, J., Carvalho, F., Cho, J. Y., Vaidyanathan, B., Yu, S., Annicelli, C., Ip, W., & Medzhitov, R. M. (2020) · Cell · doi:10.1016/j.cell.2020.02.018 · Cited by 74 · see citing works
“Consistent with this finding, chromatin accessibility of Ifng locus with T-bet binding site, which is known to be important for IFN-γ gene expression (Karmaus et al., 2019), was reduced in naïve OT-I T cells with perinatal Cell.”
Th17 cell pathogenicity in autoimmune disease
Park, E., & Ciofani, M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01535-9 · Cited by 75 · see citing works
“…stem-like TCF-1 + SLAMF6 + IL-17A + Th17 cell population as a reservoir of precursors for the generation of encephalito-genic GM-CSF + IFN γ + CXCR6 + ex-Th17 cells during EAE 54 – 56 , highlighting the dynamic nature of Th17 cell identity and effector transdifferentiation during autoimmunity.”
TCF-1 limits the formation of Tc17 cells via repression of the MAF–RORγt axis
Mielke, L. A., Liao, Y., Clemens, E. B., Firth, M. A., Duckworth, B. C., Huang, Q., Almeida, F. F., Chopin, M., Koay, H., Bell, C. A., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20181778 · Cited by 68 · see citing works
“Tcf7−/− (Verbeek et al., 1995), Id2gfp (Jackson et al., 2011), Rorc(γt)gfp (Eberl et al., 2004), c-maf−/− (Kawauchi et al., 1999), Tcf7fl/fl (Steinke et al., 2014), Cd4Cre (Sawada et al., 1994), and dLckCre (Zhang and Bevan, 2012) have been previously described and were all maintained on a C57BL/6…”
Metabolic regulation of TH17 cells
Shen, H., & Shi, L. Z. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.03.005 · Cited by 68 · see citing works
“…the development of TH1-like CD27 T-bethi TH17 cells and failed to induce autoimmune inflammation, but instead upregulated TCF-1 expression and acquired stemness-associated features, clearly supporting that mTORC1 and glycolysis control the pathogenicity of TH17 cells (Karmaus et al., 2019).”
BackgroundThe induction and function of the anti-inflammatory fate of TH17 cells
Xu, H. Y., Agalioti, T., Zhao, J., Steglich, B., Wahib, R., Vesely, M. C. A., Bielecki, P., Bailis, W., Jackson, R. P., Perez, D. R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17097-5 · Cited by 68 · see citing works
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HIV persistence in subsets of CD4+ T cells: 50 shades of reservoirs
Fromentin, R., & Chomont, N. (2020) · Seminars in Immunology · doi:10.1016/j.smim.2020.101438 · Cited by 67 · see citing works
Biological and clinical significance of T helper 17 cell plasticity
Mazzoni, A., Maggi, L., Liotta, F., Cosmi, L., & Annunziato, F. (2019) · Immunology · doi:10.1111/imm.13124 · Cited by 63 · see citing works
SU, W. W., Chapman, N. M., Wei, J., Zeng, H., Dhungana, Y., Shi, H., Saravia, J., Zhou, P., Long, L., Rankin, S. L., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.022 · Cited by 60 · see citing works
“The accession number for the ATAC-Seq data of CD4+YFP+ WT and Fntb- or Pggt1b-deficient cTreg and eTreg cells from mixed bone marrow chimeras reported in this paper is GSE158863.”
BackgroundMethodInfluentialSelf-citationMicrobiota-Propelled T Helper 17 Cells in Inflammatory Diseases and Cancer
Bellone, M., Brevi, A., & Huber, S. (2020) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00064-19 · Cited by 59 · see citing works
Yu, J., Peng, J., & Chi, H. (2019) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2019.03.003 · Cited by 60 · see citing works
Self-citationThakore, P. I., Schnell, A., Zhao, M., Huang, L., Hou, Y., Christian, E., Zaghouani, S., Wang, C., Singh, V., Ma, S., et al. (2022) · doi:10.1101/2022.02.26.482041 · Cited by 57 · see citing works
“Moreover, recent studies demonstrated an important role for BACH2 in the generation of stem-like CD8 + T cells 43,49 , and npT H 17 cells were shown to share multiple properties with stem-like CD8 + T cells, including a shared expression profile 9,13,45,61 .”
Re-defining T-Cell Exhaustion: Subset, Function, and Regulation
Im, S. J., & Ha, S. (2020) · Immune Network · doi:10.4110/in.2020.20.e2 · Cited by 56 · see citing works
“Stem cell-like T helper17 CD4 T cells (Th17) was also determined in mice with experimental autoimmune encephalomyelitis (EAE) (100).”
BackgroundRegulation of activated T cell survival in rheumatic autoimmune diseases
Rosetti, F., Madera-Salcedo, I. K., Rodríguez‐Rodríguez, N., & Crispín, J. C. (2022) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00741-9 · Cited by 53 · see citing works
Network Approaches for Dissecting the Immune System
Shi, H., Yan, K., Ding, L., Qian, C., Chi, H., & Yu, J. (2020) · iScience · doi:10.1016/j.isci.2020.101354 · Cited by 50 · see citing works
“Another study examined the activity of transcriptional factors in wild-type and Raptor (a major component of the mTOR protein complex)-deficient Th17 cells by using Ingenuity Pathway Analysis based on down-stream target-gene expression (Karmaus et al., 2019).”
MethodSelf-citationT cell metabolism in homeostasis and cancer immunity
Wei, J., Zheng, W., Chapman, N. M., Geiger, T. L., & Chi, H. (2021) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.02.003 · Cited by 50 · see citing works
Self-citationmTOR Dysregulation by Vaccinia Virus F17 Controls Multiple Processes with Varying Roles in Infection
Meade, N., King, M. W., Munger, J. C., & Walsh, D. (2019) · Journal of Virology · doi:10.1128/jvi.00784-19 · Cited by 50 · see citing works
Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization
Lee, G. R. (2023) · Immune Network · doi:10.4110/in.2023.23.e4 · Cited by 48 · see citing works
“scRNA-seq and computational analysis show that Th17 cells isolated from animal models of autoimmune diseases are heterogeneous and show a spectrum of cellular states (86,87).”
BackgroundKratchmarov, R., Djeddi, S., Dunlap, G. S., He, W., Jia, X., Burk, C. M., Ryan, T., McGill, A., Allegretti, J. R., Kataru, R. P., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01803-2 · Cited by 48 · see citing works
Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation.
Chen, C., Zhang, W., Zhou, T.-Y., Liu, Q.-Y., Han, C., Huang, Z.-H., Chen, S., Mei, Q., Zhang, C.-J., Zhang, K.-G., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111741 · Cited by 35 · see citing works
Im, S. J., Lee, K., & Ha, S. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01301-3 · Cited by 48 · see citing works
Identification of Novel Molecular Markers of Human Th17 Cells
Sałkowska, A., Karaś, K., Karwaciak, I., Walczak‐Drzewiecka, A., Krawczyk, M., Sobalska‐Kwapis, M., Dastych, J., & Ratajewski, M. (2020) · Cells · doi:10.3390/cells9071611 · Cited by 45 · see citing works
“It appears that epigenetic changes are involved in this process [92,93], and we suggest that H3K4me3 is a part of the histone code that maintains the region in an “open” state in the event that rapid activation associated with cellular plasticity is needed [94–96].”
BackgroundLipid metabolism in homeostasis and disease
Li, Z., Deng, W., Yang, L., Tang, C., Yue, J.-M., Monteiro, O., Baptista‐Hon, D. T., & Li, T. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02357-x · Cited by 51 · see citing works
“212,213 Unlike effector CD8 + T cells, central memory CD8 + T cells primarily utilize de novo synthesized triacylglycerides from glucose for FAO, which rely on lysosomal acid lipase.”
Metabolic rewiring and communication in cancer immunity
Chapman, N. M., & Chi, H. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.02.001 · Cited by 43 · see citing works
“56,93,94,239,240 In addition, single cell-based tools to predict metabolic flux, such as single cell flux estimation analysis (scFEA), Compass and MetaFlux, are emerging to identify discrete metabolic programs that dictate immune cell function.”
MethodSelf-citationMorianos, I., Trochoutsou, A. I., Papadopoulou, G., Semitekolou, M., Banos, A., Konstantopoulos, D., Manousopoulou, A., Καπασά, Μ., Wei, P. Y., Lomenick, B., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1918196117 · Cited by 39 · see citing works
Geier, C., & Perl, A. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102984 · Cited by 39 · see citing works
“Phenotypically, the mTORC1 positive TH17 subset can be distinguished by a lack of CD27 expression [53] whereas CD27 positive TH17 cells are associated with a memorylike transcriptome, express low levels of mTORC1 and are capable to proliferate and turn into CD27 negative TH17 cells.”
Doss, P. M. I. A., Umair, M., Baillargeon, J., Fazazi, R., Fudge, N., Akbar, I., Yeola, A. P., Williams, J. B., Leclercq, M., Joly-Beauparlant, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108833 · Cited by 39 · see citing works
Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans
Li, Y., Ramírez-Suástegui, C., Harris, R. J., Castañeda-Castro, F. E., Ascui, G., Pérez-Jeldres, T., Diaz, A., Morong, C., Giles, D. A., Chai, J. N., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01860-7 · Cited by 39 · see citing works
“…in animal models of autoimmune disease describe the existence of a stem-like T cell population that exhibits resistance to exhaustion, and importantly, this progenitor population sustains the pool of short-lived proinflammatory effector T cells that drive autoimmune inflammation 10–13 , 16 .”
InfluentialTonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome
Marié, I. J., Brambilla, L., Azzouz, D. F., Chen, Z., Baracho, G. V., Arnett, A., Li, H. S., Liu, W., Cimmino, L., Chattopadhyay, P. K., et al. (2021) · eLife · doi:10.7554/elife.68371 · Cited by 33 · see citing works
Metabolic rewiring: a new master of Th17 cell plasticity and heterogeneity
Papadopoulou, G., & Xanthou, G. (2021) · FEBS Journal · doi:10.1111/febs.15853 · Cited by 36 · see citing works
Fu, S., Chien, M., Hsu, C.-Y., Liu, Y., & Sytwu, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093379 · Cited by 35 · see citing works
The Ups and Downs of Metabolism during the Lifespan of a T Cell
Balyan, R., Gautam, N., & Gascoigne, N. R. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217972 · Cited by 35 · see citing works
Mangani, D., Subramanian, A., Huang, L., Cheng, H., Krovi, S. H., Wu, Y., Yang, D., Moreira, T. G., Escobar, G., Schnell, A., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.09.017 · Cited by 35 · see citing works
Wang, S.-H., Zissler, U., Buettner, M., Heine, S., Heldner, A., Kotz, S., Pechtold, L., Kau, J., Plaschke, M., Ullmann, J. T., et al. (2021) · Allergy. European Journal of Allergy and Clinical Immunology · doi:10.1111/all.14896 · Cited by 24 · see citing works
RORα is critical for mTORC1 activity in T cell-mediated colitis
Chi, X., Jin, W., Bai, X., Zhao, X., Shao, J., Li, J., Sun, Q., Su, B., Wang, X., Yang, X. O., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109682 · Cited by 33 · see citing works
Functional heterogeneity of CD4+ T cells in liver inflammation
Muscate, F., Woestemeier, A., & Gagliani, N. (2021) · Seminars in Immunopathology · doi:10.1007/s00281-021-00881-w · Cited by 32 · see citing works
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The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb
Feng, R., Liu, F., Li, R., Zhou, Z., Lin, Z., Song, L., Deng, S., Li, Y., Nong, B., Xia, Y., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00938-z · Cited by 33 · see citing works
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Wang, Y., Liu, M., Zhang, L., Liu, X., Ji, H., Wang, Y., Gui, J., Yan, Y., & Wen, Z. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06336-4 · Cited by 29 · see citing works
Beyond T-cell subsets: stemness and adaptation redefining immunity and immunotherapy
Zou, D., Li, X. C., & Chen, W. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01321-7 · Cited by 30 · see citing works
Self-citationChoi, G., Park, Y., Cho, M., Moon, H., Kim, D., Kang, C., Chung, Y., & Kim, B. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00632-9 · Cited by 28 · see citing works
Metabolic Control of Memory T-Cell Generation and StemnessPreprint
Raynor, J. L., Chapman, N. M., & Chi, H. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037770 · Cited by 28 · see citing works
“CD4+ Tfh stem-cell-like (Lüthje et al. 2012; Hale et al. 2013; Kunzli et al. 2020); CD4+ Th17 stem-cell-like (Muranski et al. 2011; Karmaus et al. 2019); CD8+ Tscm (Gattinoni et al. 2009; Sukumar et al. 2016); CD8+CX3CR1int peripheral memory (Gerlach et al. 2016); CD8+CXCR5+ Tfh-like (He et al.…”
BackgroundInfluentialSelf-citationMeyer, A., Sienes, R. E., Nijim, W., Zanotti, B., Umar, S., Volin, M. V., Raemdonck, K. V., Lewis, M., Pitzalis, C., Arami, S., et al. (2023) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2022-223284 · Cited by 26 · see citing works
Zhu, C., Boucheron, N., Al-Rubaye, O., Chung, B. K., Thorbjørnsen, L. W., Köcher, T., Schuster, M., Claudel, T., Halilbasic, E., Kunczer, V., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-333297 · Cited by 25 · see citing works
Shen, M.-Y., Wang, X., Di, Y., Zhang, M.-F., Tian, F.-X., Qian, F., Jiang, B., & Zhou, L. (2022) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2022.2086139 · Cited by 26 · see citing works
“Driven by key regulators of glycolysis, such as mTOR, pathogenic Th17 cells exhibit increased glycolysis, which may promote proliferation and pro-inflammatory cytokine production by facilitating elevated protein, lipid, and nucleic acid [40].”
BackgroundPolyamines from myeloid-derived suppressor cells promote Th17 polarization and disease progression
Hu, C., Yu, Z., Ma, Z., Zhao, L., Wu, H., Shu, C., Pang, B., Yu, J., Xu, Y., Zhang, X., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.10.013 · Cited by 25 · see citing works
“6,40 Our previous studies of SLE patients and SLE mouse models showed that MDSCs can promote Th17 differentiation and aggravate SLE progression by producing Arg-1.”
BackgroundA diverse proteome is present and enzymatically active in metabolite extracts
House, R. J., Soper-Hopper, M. T., Vincent, M. P., Ellis, A. E., Capan, C. D., Madaj, Z., Wolfrum, E., Isaguirre, C. N., Castello, C. D., Johnson, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50128-z · Cited by 25 · see citing works
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Self-citationDomizio, J. D., & Gilliet, M. F. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.04.020 · Cited by 23 · see citing works
“However, NET-induced reprogramming of memory T cells into Th17 cells should also be considered, especially in the light of the recent finding that committed memory Th cells contain a subpopulation of cells with functional plasticity (Karmaus et al., 2019).”
BackgroundTargeting Th17 cells in HIV-1 remission/cure interventions
Fert, A., Marchand, L. R., Salinas, T. R. W., & Ancuța, P. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.04.013 · Cited by 20 · see citing works
Metabolic Constrains Rule Metastasis Progression
Roda, N., Gambino, V., & Giorgio, M. (2020) · Cells · doi:10.3390/cells9092081 · Cited by 21 · see citing works
Th17 cells in the liver: balancing autoimmunity and pathogen defense
Taniki, N., Nakamoto, N., Chu, P., Ichikawa, M., Teratani, T., & Kanai∥, T. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00917-9 · Cited by 21 · see citing works
“The glycolytic-lipogenic pathway is not only important to Th17 differentiation, but also controls the pathogenicity, stemness, and plasticity of Th17 cell [143].”
BackgroundByström, J., Taher, T. E. I., Henson, S. M., Gould, D., & Mageed, R. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.990794 · Cited by 21 · see citing works
“Furthermore, mice with T cells lacking Raptor produced Th17 cells with low metabolic activity, and expression of TCF1 (Figure 1D) (6).”
BackgroundPIM kinases regulate early human Th17 cell differentiation
Buchacher, T., Shetty, A., Koskela, S. A., Smolander, J., Kaukonen, R., Sousa, A. G. G., Junttila, S., Laiho, A., Rundquist, O., Lönnberg, T., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113469 · Cited by 21 · see citing works
Stem‐like T cells in cancer and autoimmunity
Schnell, A. (2024) · Immunological Reviews · doi:10.1111/imr.13356 · Cited by 22 · see citing works
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“Moreover, in an experimental autoimmune encephalomyelitis (EAE) mouse model, a similar subset of TCF1+ cells was able to differentiate into Th17 cells that produced IL17 when the mTORC1 pathway was blocked (72).”
BackgroundFactors impacting the benefits and pathogenicity of Th17 cells in the tumor microenvironment
Xing, J., Man, C., Liu, Y., Zhang, Z., & Peng, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1224269 · Cited by 21 · see citing works
“Considering the significant impact of metabolism on the plasticity of Th17 cells, the emerging trend in cancer treatment is the development of suitable antitumor Th17 cells for adoptive cell therapy (88).”
BackgroundMemory like NK cells display stem cell like properties after Zika virus infection
Kujur, W., Murillo, O., Adduri, S., Vankayalapati, R., Konduru, N. V., & Mulik, S. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1009132 · Cited by 20 · see citing works
“Notably, PD1 CXCR5 CD8 T cells in chronic viral infection [11–13,48,49] and progenitor exhausted CD8 T cells from the tumors [14,15] as well as CD27 Th17 cells from autoimmune disease [36] display stemness.”
BackgroundDecoding the crosstalk between mevalonate metabolism and T cell function
Kennewick, K. T., & Bensinger, S. J. (2023) · Immunological Reviews · doi:10.1111/imr.13200 · Cited by 20 · see citing works
Immunometabolism of dendritic cells in health and disease
Guo, C., & Chi, H. (2023) · Advances in immunology · doi:10.1016/bs.ai.2023.10.002 · Cited by 20 · see citing works
Self-citation
- Authors
- Karmaus, P. W. F., Chen, X., Lim, S. A., Herrada, A. A., Nguyen, T.-L. M., Xu, B., Dhungana, Y., Rankin, S., Chen, W., Rosencrance, C., Yang, K., Fan, Y., Cheng, Y., Easton, J., Neale, G., Vogel, P., & Chi, H.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Chi, Hongbo
- ORCID
- Venue
- Nature
- Published
- 2018-12-19
- Volume
- 565
- Issue
- 7737
- Pages
- 101-105
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6420879
- OpenAlex
- W2905426112
- Semantic Scholar
- ebe01d7ca54b23c200f359ee77ec3f9d963ffe99
- Cited by
- 215
- References
- 42
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 37 · 2023: 24 · 2022: 21 · 2021: 32 · 2020: 35 · 2019: 17 · 2017: 1
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- St. Jude Children's Research Hospital
- National Institutes of Health
- National Cancer Institute (R01CA176624, R01CA221290, P30CA021765)
- National Institute of Allergy and Infectious Diseases (R01AI101407, R01AI105887, R01AI140761, R01AI131703, R37AI105887)
- National Institute of Neurological Disorders and Stroke (R01NS064599)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- Th17 cells, T cell stemness, T cell plasticity, mTORC1 signaling, TCF1, T-bet, CD27, anabolic metabolism, autoimmune neuroinflammation, chronic autoimmune disease, single-cell RNA sequencing
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR, T-bet Transcription Factor, Animals, Autoimmune Diseases, Disease Models, Animal, Female, Immunologic Memory, Inflammation, Male, Stem Cells, Signal Transduction, Sequence Analysis, RNA, Tumor Necrosis Factor Receptor Superfamily, Member 7, T-Box Domain Proteins, Mice, T Cell Transcription Factor 1, Cell Transdifferentiation, Th17 Cells, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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