The DOI matches its Crossref record; 151 of the 151 references it cites were found in a registry or an index.
The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2
Abstract
The mononuclear phagocytes control the body homeostasis through the involvement in resolving tissue injury and further wound healing. Indeed, local tissue microenvironmental changes can significantly influence the functional behavior of monocytes and macrophages. Such microenvironmental changes for example occur in an atherosclerotic plaque during all progression stages. In response to exogenous stimuli, macrophages show a great phenotypic plasticity and heterogeneity. Exposure of monocytes to inflammatory or anti-inflammatory conditions also induces predominant differentiation to proinflammatory (M1) or anti-inflammatory (M2) macrophage subsets and phenotype switch between macrophage subsets. The phenotype transition is accompanied with great changes in the macrophage transcriptome and regulatory networks. Interferon-regulatory factors (IRFs) play a key role in hematopoietic development of monocytes, their differentiation to macrophages, and regulating macrophage maturation, phenotypic polarization, phenotypic switch, and function. Of 9 IRFs, at least 3 (IRF-1, IRF-5, and IRF-8) are involved in the commitment of proinflammatory M1 whereas IRF-3 and IRF-4 control M2 polarization. The role of IRF-2 is context-dependent. The IRF impact on macrophage phenotype plasticity and heterogeneity is complex and involves activating and repressive function in triggering transcription of target genes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“IRF-5 is critically involved in M1- macrophage polarization (42)”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [42]
In the citing paper
“which possesses phagocytic capacity, and the ability to secrete reactive nitrogen and oxygen species and pro-inflammatory cytokines such as IL-6, IL-12, IL-23 and TNF-α, which in turn promote CD8+ T cell and NK cell cytotoxicity.”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [42]
Citations
Cites
1 retracted
Chistiakov, D. A., Bobryshev, Y. V., Nikiforov, N. G., Elizova, N. V., Sobenin, I. A., & Orekhov, A. N. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.03.055 · Cited by 184
RetractedMacrophage activation and polarization: nomenclature and experimental guidelines
Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.008 · Cited by 6,337
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
Geissmann, F., Jung, S., & Littman, D. R. (2003) · Immunity · doi:10.1016/s1074-7613(03)00174-2 · Cited by 3,504
Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway
Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., et al. (2003) · Science · doi:10.1126/science.1087262 · Cited by 3,286
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759
Martínez, F. O., Gordon, S., Locati, M., & Mantovani, A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.10.7303 · Cited by 2,399
Transcriptional regulation of macrophage polarization: enabling diversity with identity
Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284
Molecular Mechanisms That Influence the Macrophage M1–M2 Polarization Balance
Wang, N., Liang, H., & Zen, K. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00614 · Cited by 2,069
Blood Monocytes: Development, Heterogeneity, and Relationship with Dendritic Cells
Auffray, C., Sieweke, M. H., & Geissmann, F. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132557 · Cited by 1,745
Tacke, F., Alvarez, D., Kaplan, T. J., Jakubzick, C., Spanbroek, R., Llodra, J., Garin, A., Liu, J., Mack, M., van Rooijen, N., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28549 · Cited by 1,323
Flagged first, then by citations
Research works printed but not linked: 1
- Fleetwood, 2007, Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation, J. Immunol., 178, 5245, 10.4049/jimmunol.178.8.5245 · DOI · Paper page
Cited by
Sorted by citations
Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers
Zhang, F., Parayath, N. N., Ene, C., Stephan, S. B., Koehne, A. L., Coon, M. E., Holland, E. C., & Stephan, M. T. (2019) · Nature Communications · doi:10.1038/s41467-019-11911-5 · Cited by 527
Macrophage plasticity: signaling pathways, tissue repair, and regeneration
Yan, L., Wang, J., Cai, X., Liou, Y., Shen, H., Hao, J., Huang, C., Luo, G., & He, W. (2024) · MedComm · doi:10.1002/mco2.658 · Cited by 406
M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds
Wang, Y., Smith, W. W., Hao, D., He, B., & Kong, L. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.02.050 · Cited by 330
Alternatively activated macrophages; a double-edged sword in allergic asthma
Abdelaziz, M. H., Abdelwahab, S. F., Wan, J., Cai, W., Wang, H., Cheng, J., Kesavan, D. K., Vasudevan, A., Sadek, A., Su, Z., et al. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02251-w · Cited by 289
Macrophage Polarization in the Development and Progression of Ovarian Cancers: An Overview
Cheng, H., Wang, Z., Fu, L., & Xu, T. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00421 · Cited by 268
“In addition, interferon regulatory factor (IRF)-1, IRF-5, and IRF-8 are correlated with polarization to the M1 phenotype, while IRF3 and IRF-4 polarize cells to the M2 phenotype (48).”
BackgroundMacrophage Polarization in Leishmaniasis: Broadening Horizons
Tomiotto‐Pellissier, F., Bortoleti, B. T. D. S., Assolini, J. P., Gonçalves, M. D., Carloto, A. C. M., Miranda-Sapla, M. M., Costa, I. C., Bordignon, J., & Pavanelli, W. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02529 · Cited by 239
“IRF4 and IRF5 are involved in the polarization of M1 and M2 macrophages, but the role of IRFs in M2 polarization is not completely clear (44).”
BackgroundZeng, J., Bao, T., Yang, K., Zhu, X., Wang, S., Xiang, W., Ge, A., Zeng, L., & Ge, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1047550 · Cited by 175
Type I interferon signaling, regulation and gene stimulation in chronic virus infection
Lukhele, S., Boukhaled, G. M., & Brooks, D. G. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.05.001 · Cited by 173
“In addition, unlike IRFs 1, 5 and 8, which are associated with polarization towards M1 macrophage phenotype, IRF4 is involved in skewing towards the anti-inflammatory M2 phenotype (80).”
BackgroundTargeting of TAMs: can we be more clever than cancer cells?
Kzhyshkowska, J. G., Shen, J., & Larionova, I. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01232-z · Cited by 187
“IRF3 promotes M-CSF-mediated differentiation of monocytes toward M2-type macrophages; inhibits the expression of proin fl ammatory genes (IL-1 α , IL-1 β , TNF α , IL-6, IL-8, and CXCL1); and stimulates the expression of protumoral IL-10 and IFN-β [292, 295].”
Slevin, E., Baiocchi, L., Wu, N., Ekser, B., Sato, K., Lin, E. P.-Y., Ceci, L., Chen, L., Ramos‐Lorenzo, S., Xu, W., et al. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.08.014 · Cited by 173
Vidyarthi, A., Khan, N., Agnihotri, T., Negi, S., Das, D. K., Aqdas, M., Chatterjee, D., Colegio, O. R., Tewari, M. K., & Agrewala, J. N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01650 · Cited by 163
Targeting interferon-γ in hyperinflammation: opportunities and challenges
Benedetti, F. D., Prencipe, G., Bracaglia, C., Marasco, E., & Grom, A. A. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00694-z · Cited by 158
Li, Z., Li, Q., Tong, K., Zhu, J., Zhang, H., Chen, B., & Chen, L. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02975-0 · Cited by 157
“This process is called macrophage polarization [52].”
Macrophages with regulatory functions, a possible new therapeutic perspective in autoimmune diseases
Benedetto, P. D., Ruscitti, P., Vadasz, Z., Toubi, E., & Giacomelli, R. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.102369 · Cited by 140
Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages
Larionova, I., Kazakova, E., Patysheva, M. R., & Kzhyshkowska, J. G. (2020) · Cancers · doi:10.3390/cancers12061411 · Cited by 126
“IRF3 promotes M-CSF-mediated differentiation of monocytes toward M2 type macrophages [25].”
BackgroundKoh, Y., Yang, G., Lai, C., Weerawatanakorn, M., & Pan, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082208 · Cited by 127
“Nine IRFs have been identified, with three of them (IRF-1, IRF-5, and IRF-8) being normally associated with the polarization mechanism of M1 macrophages, while IRF-3 and -4 are more often found to be involved in M2 polarization [57].”
BackgroundGast, M., Rauch, B. H., Haghikia, A., Nakagawa, S., Haas, J., Stroux, A., Schmidt, D., Schumann, P. A., Weiß, S., Jensen, L., et al. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz085 · Cited by 122
Epigenetic regulation of macrophage polarization in wound healing
Chen, C., Liu, T., Tang, Y., Luo, G., Liang, G., & He, W. (2023) · Burns & Trauma · doi:10.1093/burnst/tkac057 · Cited by 130
Hepatitis B virus-induced modulation of liver macrophage function promotes hepatocyte infection
Faure‐Dupuy, S., Delphin, M., Aillot, L., Dimier, L., Lebossé, F., Fresquet, J., Parent, R., Matter, M. S., Rivoire, M. L., Bendriss‐Vermare, N., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.06.032 · Cited by 109
Korf, H., du Plessis, J., van Pelt, J. F., Groote, S. D., Cassiman, D. M., Verbeke, L., Ghesquière, B., Fendt, S., Bird, M., Talebi, A., et al. (2018) · Gut · doi:10.1136/gutjnl-2018-316888 · Cited by 101
Thibaut, R., Gage, M., Pineda‐Torra, I., Chabrier, G., Venteclef, N., & Alzaïd, F. (2021) · FEBS Journal · doi:10.1111/febs.15877 · Cited by 97
Xiong, T., Yang, K., Zhao, T., Zhao, H., Gao, X., You, Z., Fan, C., Kang, X., Yang, W., Zhuang, Y., et al. (2023) · Advanced Science · doi:10.1002/advs.202205997 · Cited by 89
Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions
Xu, G.-X., Song, W., Yu, C., Zhao, S., Yang, W., Feng, Y.-H., Pan, C., Kun-xing, Y., & Ma, Y. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1199519 · Cited by 93
“A growing body of literature shows that IRFs can also influence the phenotype and polarization of both KCs and macrophages (Chistiakov et al., 2018).”
BackgroundMerecz-Sadowska, A., Sitarek, P., Śliwiński, T., & Zajdel, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249605 · Cited by 93
“In monocyte-derived macrophages, stimulation of IRF-5 expression is induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) [128].”
BackgroundMacrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
Peng, M., Li, N., Wang, H., Li, Y., Liu, H., Luo, Y., Lang, B., Zhang, W., Li, S., Tian, L., et al. (2025) · MedComm · doi:10.1002/mco2.70304 · Cited by 98
“IRFs play a crucial role in hematopoietic development, differentiation into macrophages, and regulation of macrophage maturation, phenotype polarization, phenotype switching, and function [104].”
Effects of Environmental pH on Macrophage Polarization and Osteoimmunomodulation
Wu, H. P., Yin, Y., Hu, X., Peng, C., Liu, Y., Li, Q., Huang, W., & Huang, Q. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01181 · Cited by 85
Kwon, D. H., Lee, H., Park, C., Hong, S. H., Hong, S. H., Kim, G., Cha, H., Kim, S., Kim, H., Hwang, H., et al. (2019) · Antioxidants · doi:10.3390/antiox8090413 · Cited by 87
“The phenotype transition is involved alteration of the macrophage transcriptome and regulatory networks [33].”
BackgroundAirway hyperresponsiveness development and the toxicity of PM2.5
Lu, X., Li, R., & Yan, X. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-020-12051-w · Cited by 83
Recent advances in nanomedicines for regulation of macrophages in wound healing
Joorabloo, A., & Liu, T. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01616-1 · Cited by 82
Macrophage Polarization: An Important Candidate Regulator for Lung Diseases
Deng, L., Jian, Z., Xu, T., Li, F., Deng, H., Zhou, Y., Lai, S., Xu, Z., & Zhu, L. (2023) · Molecules · doi:10.3390/molecules28052379 · Cited by 85
The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming
Luque-Campos, N., Bustamante-Barrientos, F. A., Pradenas, C., García, C., Araya, M. J., Bohaud, C., Contreras-López, R., Elizondo-Vega, R., Djouad, F., Luz-Crawford, P., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.624746 · Cited by 82
“Also, MSCs enhance interferon-regulatory factor-4 (IRF-4) expression levels (100), which participate in M2 macrophage polarization by inducing Arg1, mannose receptor, Ym1, and FIZZ1 expression (102).”
BackgroundSittplangkoon, C., Alameh, M.-G., Weissman, D., Lin, P. J. C., Tam, Y. K., Prompetchara, E., & Palaga, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.983000 · Cited by 79
“IRF-5 is critically involved in M1- macrophage polarization (42), which possesses phagocytic capacity, and the ability to secrete reactive nitrogen and oxygen species and pro-inflammatory cytokines such as IL-6, IL-12, IL-23 and TNF-a, which in turn promote CD8 T cell and NK cell cytotoxicity.”
BackgroundGao, J., Ao, Y.-Q., Zhang, L.-X., Deng, J., Wang, S., Wang, H., Jiang, J.-H., & Ding, J. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02505-z · Cited by 79
“Previous studies had identified IRF4 as an important mediator of M2 polarization of macrophages [21], suggesting that ELF4 could elicit M2 polarization of macrophages via activation of IRF4.”
ResultMacrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease
Du, Y., Rong, L., Cong, Y., Shen, L., Zhang, N., & Wang, B. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.1901079 · Cited by 81
“However, under certain circumstances, emodin can inhibit the activation of STAT6 and IRF4 signals while suppressing the polarization of M1 macrophages, thereby reducing the response of macrophages to M1 and M2 stimuli [197].”
BackgroundInfluentialMa, S., Zhang, J., Liu, H., Li, S., & Wang, Q. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.896591 · Cited by 81
Tumor-Associated Macrophages as Major Immunosuppressive Cells in the Tumor Microenvironment
Ghebremedhin, A., Athavale, D., Zhang, Y.-T. Y., Yao, X., Balch, C., & Song, S. (2024) · Cancers · doi:10.3390/cancers16193410 · Cited by 79
“Moreover, the involvement of interferon regulatory factors (IRFs) is notable, with IRF-1, IRF-5, and IRF-8 favoring M1-like polarization, while IRF-3 and IRF-4 promote the M2-like phenotype [28].”
BackgroundShi, Q., Zhao, L., Xu, C., Zhang, L., & Zhao, H. (2019) · Molecules · doi:10.3390/molecules24091766 · Cited by 68
“On the contrary, M2 macrophages are stimulated by various factors—such as macrophage colony stimulating factor (M-CSF), interleukin 4 (IL-4), IL-13, and transforming growth factor-β (TGF-β)—and participate in the resolution of inflammation and tissue repair partially through the production of anti-inflammatory factors…”
BackgroundLi, T., García-Gómez, A., Morante-Palacios, O., Ciudad, L., Özkaramehmet, S., Dijck, E. V., Rodríguez‐Ubreva, J., Vaquero, A., & Ballestar, E. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1127 · Cited by 70
Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Zhang, Y., Aldo, P. B., You, Y., Ding, J., Kaislasuo, J., Petersen, J. F., Løkkegaard, E., Peng, G., Paidas, M. J., Simpson, S., et al. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.1a0420-012rr · Cited by 67
GRaNIE and GRaNPA: inference and evaluation of enhancer‐mediated gene regulatory networks
Kamal, A., Arnold, C., Claringbould, A., Moussa, R., Servaas, N. H., Kholmatov, M. M., Daga, N., Nogina, D., Müller‐Dott, S., Reyes‐Palomares, A., et al. (2023) · Molecular Systems Biology · doi:10.15252/msb.202311627 · Cited by 69
“IRF8 is a known pro-inflammatory interferon response factor, associated with the pro-inflammatory (M1) polarisation of macrophages (Chistiakov et al , 2018), which we confirmed in our data using gene set enrichment analysis (GSEA) of the IRF8 regulon (Appendix Fig S18).”
ResultLi, X., Yao, X., Zhu, Y., Zhang, H., Wang, H., Ma, Q., Yan, F., Yang, Y., Zhang, J., Shi, H., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01824 · Cited by 57
van Puffelen, J. H., Novakovic, B., van Emst, L., Kooper, D., Zuiverloon, T. C. M., Oldenhof, U. T. H., Witjes, J. A., Galesloot, T. E., Vrieling, A., Aben, K. K. H., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005518 · Cited by 58
“Open access”
miR‐130b‐3p regulates M1 macrophage polarization via targeting IRF1
Guo, Q., Zhu, X., Wei, R., Zhao, L., Zhang, Z., Yin, X., Zhang, Y., Chu, C., Wang, B., & Li, X. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29987 · Cited by 54
“Among these transcription factors, IRF1 has been found to play significant roles in macrophage polarization (Chistiakov et al., 2018; Gunthner & Anders, 2013).”
BackgroundKowara, M., & Cudnoch‐Jędrzejewska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073513 · Cited by 54
“The M1/M2 macrophage balance within the plaque depends also on transcription factors such as interferon-regulatory factors (IRF)—IRF3 promotes macrophage polarization towards the M2 phenotype (by phosphoinositide kinase 3 (PI3K)/ protein kinase B (Akt) signaling), whereas M5 induces macrophage polarization towards the…”
BackgroundVidela, L. A., Valenzuela, R., del Campo, A., & Zúñiga‐Hernández, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115528 · Cited by 53
“…in the transformation of KCs expressing the proinflammatory phenotype M1 towards the pro-resolving or immune-modulating phenotype M2, which regulates late repair processes, resolution of inflammation and induction of immune tolerance, necessary steps at the beginning of tissue regeneration [9,10].”
BackgroundNanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects
Banerjee, K., Madhyastha, R., Nakajima, Y., Maruyama, M., & Madhyastha, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094748 · Cited by 53
“TLRs team up with immunoglobulin G (IgG) complexes to stimulate the macrophage cells to produce immunosuppressive IL-10 and TGF-β1 [59].”
BackgroundInfluentialWang, Z., Zhao, Y., Phipps‐Green, A. J., Liu‐Bryan, R., Čeponis, A., Boyle, D. L., Wang, J., Merriman, T. R., Wang, W., & Terkeltaub, R. A. (2019) · Arthritis & Rheumatology · doi:10.1002/art.41173 · Cited by 48
“Examples of hypomethylated TF motifs included the circadian clock regulators CLOCK and ARNT (for aryl hydrocarbon nuclear receptor) and genes encoding STAT2 and multiple components of AP1 (for activator protein 1), IRF1 (for interferon regulatory transcription factor 1) (34), and NFATC2 and NFATC3.”
BackgroundKang, S. A., Park, M.-K., Park, S. K., Choi, J. H., Lee, D. I., Song, S. M., & Yu, H. S. (2019) · Scientific Reports · doi:10.1038/s41598-019-43057-1 · Cited by 50
The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas
Pham, L. V., Pogue, E., & Ford, R. J. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00147 · Cited by 49
“Am J Clin Pathol (2004) 122(5):794–801.”
BackgroundInfluentialHuang, Q., Li, L., Chen, H., Liu, Q., & Wang, Z. (2019) · Nutrients · doi:10.3390/nu11071480 · Cited by 48
“There are mainly two subtypes, namely classical polarization (M1 type) or alternating polarization (M2 type) [36,37].”
BackgroundAlpha-1 Antitrypsin Attenuates M1 Microglia-Mediated Neuroinflammation in Retinal Degeneration
Zhou, T., Huang, Z., Zhu, X., Sun, X., Liu, Y., Cheng, B., Li, M., Liu, Y., He, C., & Liu, X. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01202 · Cited by 45
“IRF8 could induce the expressions of a large panel of M1-related genes, such as IFN-β, IL-12, iNOS, and so on (40, 41), whereas IRF4 functions as a negative regulator of TLRs signaling, associated with the polarization to M2 state (41, 42).”
BackgroundCampos, A. C. P., Kikuchi, D. S., Paschoa, A. F. N., Kuroki, M. A., Fonoff, E. T., Hamani, C., Pagano, R. L., & Hernandes, M. S. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00784-3 · Cited by 45
Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines
Eom, J., Yoo, J., Kim, J. J., Lee, J.-B., Choi, W., Park, C. G., & Seo, J.-Y. (2018) · Immune Network · doi:10.4110/in.2018.18.e32 · Cited by 44
Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization
Xia, W., Lu, Z., Chen, W., Zhou, J., & Zhao, Y. F. (2022) · BMC Gastroenterology · doi:10.1186/s12876-022-02146-8 · Cited by 44
Yu, S., Ding, L., Liang, D., & Luo, L. (2018) · Molecular Oral Microbiology · doi:10.1111/omi.12241 · Cited by 45
Yao, X., Dong, G., Zhu, Y., Yan, F., Zhang, H., Ma, Q., Fu, X., Li, X., Zhang, Q., Zhang, J., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00215 · Cited by 44
Johnson, C. S. C., Shively, C. A., Michalson, K. T., Lea, A. J., DeBo, R. J., Howard, T. D., Hawkins, G. A., Appt, S. E., Liu, Y., McCall, C. E., et al. (2021) · eLife · doi:10.7554/elife.68293 · Cited by 49
“…the genes encoding for seven of these 35 transcription factors, including IRF3, IRF8, MEF2C, and SP1, which drive monocyte fate and polarization in response to extracellular signals (Chistiakov et al., 2018; Günthner and Anders, 2013; Schüler et al., 2008; Scott et al., 1994; Zhang et al., 1994).”
InfluentialHan, C., Sheng, Y., Wang, J., Zhou, X., Li, W., Zhang, C., Guo, L., & Yang, Y. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108361 · Cited by 44
Alveolar macrophages: Achilles’ heel of SARS-CoV-2 infection
Wang, Z., Li, S., & Huang, B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01106-8 · Cited by 48
Hou, Y., Witte, F., Li, J., & Guan, S. (2022) · Smart Materials in Medicine · doi:10.1016/j.smaim.2022.01.001 · Cited by 43
de Sousa, J. R., Vasconcelos, P. F. D. C., & Quaresma, J. A. S. (2019) · Infection and Drug Resistance · doi:10.2147/idr.s208576 · Cited by 48
“85, 86 It is noteworthy that transcriptome analysis has enabled elucidation of mechanisms underlying the modulation of IL-4 intracellular signaling by the induction of zinc finger TFs, Egr2, and c-Myc expression.”
BackgroundSchroder, W. A., Hirata, T. D. C., Le, T. T., Gardner, J., Boyle, G. M., Ellis, J. J., Nakayama, E., Pathirana, D., Nakaya, H. I., & Suhrbier, A. (2019) · Scientific Reports · doi:10.1038/s41598-019-48741-w · Cited by 43
Transcriptional control of metabolism by interferon regulatory factors
Ahmad, Z., Kahloan, W., & Rosen, E. D. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00990-0 · Cited by 45
“IRF3, in general, drives the expression of pro-inflammatory genes and thus pushes macrophages towards an M1-like phenotype 80,81 .”
Interferon-Responsive Genes Are Targeted during the Establishment of Human Cytomegalovirus Latency
Elder, E., Krishna, B. A., Williamson, J. C., Lim, E. Y., Poole, E. L., Sedikides, G. X., Wills, M. R., O’Connor, C. M., Lehner, P. J., & Sinclair, J. H. (2019) · mBio · doi:10.1128/mbio.02574-19 · Cited by 45
“the polarization of the monocyte (71, 72) or perhaps to avoid the antiviral activities of”
BackgroundBerberine regulates PADI4-related macrophage function to prevent lung cancer
Gu, W., Zhang, M., Gao, F., Niu, Y., Sun, L., Xia, H., Li, W., Zhang, Y., Guo, Z., & Du, G. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108965 · Cited by 41
Wei, Y., Peng, N., Deng, C., Zhao, F., Tian, J., Tang, Y., Yu, S., Chen, Y., Xue, Y., Xiao, F., et al. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00943-5 · Cited by 41
“IRF4, a member of the interferon regulatory family of transcription factors, was found to be essential for maintaining the differentiation and homeostasis of various immune cell subsets, including dendritic cells and macrophages [16, 17].”
BackgroundWu, Y., Wu, B., Zhang, Z., Lu, H., Fan, C., Qi, Q., Gao, Y., Li, H., Feng, C., Zuo, J., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202000313rr · Cited by 42
Aiello, S., Podestà, M. A., Ordonez, P. Y. R., Pezzuto, F., Azzollini, N., Solini, S., Carrara, C., Todeschini, M., Casiraghi, F., Noris, M., et al. (2020) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019080778 · Cited by 40
Regulation of Hepatic Inflammation via Macrophage Cell Death
Li, Z., & Weinman, S. A. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1670674 · Cited by 43
Sindhu, S. T. A. K., Thomas, R., Kochumon, S., Wilson, A., Abu‐Farha, M., Bennakhi, A., Al‐Mulla, F., & Ahmad, R. (2019) · Cells · doi:10.3390/cells8111418 · Cited by 42
The role of natural products targeting macrophage polarization in sepsis-induced lung injury
Li, Y., Ai, S., Li, Y., Ye, W., Li, R., Xu, X., & Liu, Q. (2025) · Chinese Medicine · doi:10.1186/s13020-025-01067-4 · Cited by 40
Korytář, T., Wiegertjes, G. F., Zusková, E., Tomanová, A., Lisnerová, M., Patra, S., Sieranski, V., Šíma, R., Born‐Torrijos, A., Wentzel, A. S., et al. (2019) · Parasites & Vectors · doi:10.1186/s13071-019-3462-3 · Cited by 39
Guo, M., Yan, R., Yao, H., Duan, L., Sun, M., Xue, Z., & Jia, Y. (2019) · Mediators of Inflammation · doi:10.1155/2019/2917128 · Cited by 39
Macrophages in Bone Homeostasis
Kong, L., Wang, Y., Smith, W. W., & Hao, D. (2019) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x14666190214163815 · Cited by 37
Core-shell nanotherapeutics with leukocyte membrane camouflage for biomedical applications
Fan, M., & Jiang, M. (2020) · Journal of drug targeting · doi:10.1080/1061186x.2020.1757102 · Cited by 37
“For example, M2 macrophages can be transformed into M1 macrophages following LPS stimulation to promote inflammatory response [34,35].”
Baradaran, A., Asadzadeh, Z., Hemmat, N., Baghbanzadeh, A., Shadbad, M. A., Khosravi, N., Derakhshani, A., Alemohammad, H., Nour, M. A., Safarpour, H., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112588 · Cited by 37
RetractedWolf, S., Rannikko, J. H., Virtakoivu, R., Cinelli, P., Felmerer, G., Burger, A. E., Giovanoli, P., Detmar, M. J., Lindenblatt, N., Hollmén, M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1004609 · Cited by 36
“On the other hand, typical M1 markers were significantly downregulated: IL1b, IL6, IL23a, IL1R1 (28) and genes that inhibit M2 macrophage polarization showed reduced expression, such as TNFAIP8 (29), TLR4 (30) and IRF-1 (31).”
BackgroundKang, L., Pang, J., Zhang, X., Liu, Y., Wu, Y., Wang, J., & Han, D. (2023) · Journal of Nutrition · doi:10.1016/j.tjnut.2023.09.012 · Cited by 37
The Regulatory Network of Transcription Factors in Macrophage Polarization
Liu, J., Wang, M., & Zhao, Y. X. (2025) · ImmunoTargets and Therapy · doi:10.2147/itt.s494550 · Cited by 38
Hardman, J. A., Muneeb, F., Pople, J., Bhogal, R. K., Shahmalak, A., & Paus, R. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.04.026 · Cited by 35
Zhao, R., Cao, J., Yang, X., Zhang, Q., Iqbal, M. Z., Lü, J., & Kong, X. (2021) · Biomaterials Science · doi:10.1039/d1bm00508a · Cited by 35
Use of Nanoformulation to Target Macrophages for Disease Treatment
Liu, X., Xie, X., Jiang, J., Lin, M. J., Zheng, E., Qiu, W., Yeung, I., Zhu, M., Li, Q., Xia, T., et al. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202104487 · Cited by 36
Chen, X., Lai, Y., Song, X., Wu, J., Wang, L., Zhang, H., Liu, Z., & Wang, Y. (2018) · International Journal of Immunopathology and Pharmacology · doi:10.1177/2058738418780593 · Cited by 35
Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact
Schober, M. E., Requena, D. F., Casper, T. C., Velhorst, A. K., Lolofie, A., McFarlane, K. E., Otto, T. E., Terry, C. R., & Gensel, J. C. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.112971 · Cited by 35
“(Chistiakov et al., 2018) Irf8 expression is necessary for microgliogenesis.”
Neoadjuvant therapy alters the immune microenvironment in pancreatic cancer
Zhang, H., Ye, L., Yu, X., Jin, K., & Wu, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.956984 · Cited by 34
“IRF-5 is a transcription factor that has been shown to have tumor suppression functions and plays a central role in regulating TAM polarization (59, 60).”
BackgroundInterferon-stimulated genes: new platforms and computational approaches
Green, R. R., Ireton, R. C., & Gale, M. (2018) · Mammalian Genome · doi:10.1007/s00335-018-9755-6 · Cited by 37
Harnessing myeloid cells in cancer
Park, S., Pylaeva, E., Bhuria, V., Gambardella, A. R., Schiavoni, G., Mougiakakos, D., Kim, S.-H., & Jabłońska, J. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02249-2 · Cited by 35
Bastea, L. I., Liou, G., Pandey, V., Martinez, A. K. F., Roemeling, C. A. V., Döppler, H. R., Li, Z., Qiu, Y., Edenfield, B. H., Copland, J. A., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-1153 · Cited by 32
“Interferon regulatory factors play key roles in hematopoietic development of monocytes and their differentiation into macrophages, but also in regulating polarization phenotype and phenotype switching (36).”
BackgroundFaass, L., Stein, S. C., Hauke, M., Gapp, M., Albanese, M., & Josenhans, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.632154 · Cited by 32
“A trend to differentiation towards a proin fl ammatory M1 macrophage phenotype was also supported by the transcriptome results (see below), which showed an increased expression of M1-related upstream activator and M1-speci fi c transcription factor genes such as STAT1, STAT2, and AP-1 (64) as well as IRF5 (62), while M2…”
InfluentialSharifiaghdam, M., Shaabani, E., Sharifiaghdam, Z., Keersmaecker, H. D., Lucas, B., Lammens, J., Ghanbari, H., Teimoori‐Toolabi, L., Vervaet, C., Beer, T. D., et al. (2021) · Nanoscale · doi:10.1039/d1nr03830c · Cited by 32
The Roles of Monocytes and Macrophages in Behçet’s Disease With Focus on M1 and M2 Polarization
Hirahara, L., Takase‐Minegishi, K., Kirino, Y., Iizuka-Iribe, Y., Soejima, Y., Yoshimi, R., & Nakajima, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.852297 · Cited by 32
“IRF8 is also involved in the formation of M1 macrophages (63).”
BackgroundNLRP3 Inflammasome in Atherosclerosis: Putting Out the Fire of Inflammation
Shao, B., Xu, H., Zhao, Y.-C., Zheng, X.-R., Wang, F., & Zhao, G.-R. (2022) · Inflammation · doi:10.1007/s10753-022-01725-x · Cited by 34
“Furthermore, the inducing formation of the anti-inflammatory phenotype of macrophages (M2 phenotype) was shown to attenuate inflammatory reaction, which serves as an effective way to alleviate AS [62, 63].”
BackgroundValenzuela, R., Farías, C., Muñoz, Y., Zúñiga‐Hernández, J., & Videla, L. A. (2025) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2025.112676 · Cited by 36
Macrophage-mediated cancer drug delivery
Wang, H., Liu, Y., Yang, G., & Zhao, C. (2020) · Materials Today Sustainability · doi:10.1016/j.mtsust.2020.100055 · Cited by 31
In vitro inhibition of tumor growth by low-dose iron oxide nanoparticles activating macrophages
Zhang, L., Tan, S., Liu, Y., Xie, H., Luo, B., & Wang, J. (2019) · Journal of Biomaterials Applications · doi:10.1177/0885328218817939 · Cited by 31
Serrano, C., Galán, S., Rubio, J. F., Candelario‐Martínez, A., Montes-Gómez, A. E., Chánez-Paredes, S. D., Cedillo‐Barrón, L., Michael Schnoor, A., Meraz‐Ríos, M. A., Villegas‐Sepúlveda, N., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801060 · Cited by 29
“For example, IFN-g induces a sequential activation of STAT1 and STAT3 in the same epithelial cell, something similar to the observed during priming of immune cells by IFN-g (43, 44).”
ResultZheng, L., Wei, L., Zhu, D., Li, Z., & Kong, L. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900053 · Cited by 29
“Compared with the WT group, clodronate liposomes, and clodronate liposomes + WT mø groups at 1 h after IR, M1-related markers (IL-1b, IL-6, and TNF-a) and cytokines (IL-6 and TNF-a) in the clodronate liposomes + si-Roquin-1 mø group were significantly elevated; M2 markers (IL-10, IL-13, Arg-1, and PPARg) and cytokines…”
BackgroundMatsuki, H., Hiroshima, Y., Miyake, K., Murakami, T., Homma, Y., Matsuyama, R., Morioka, D., Kurotaki, D., Tamura, T., & Endo, I. (2020) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.883 · Cited by 30
Luo, Q., Luo, J., & Wang, Y. (2020) · Journal of Inflammation Research · doi:10.2147/jir.s288244 · Cited by 28
Role of amino acid metabolism in tumor immune microenvironment of colorectal cancer
Zhu, M. (2025) · American Journal of Cancer Research · doi:10.62347/zsoo2247 · Cited by 27
Metadata
- Authors
- Chistiakov, D. A., Myasoedova, V. A., Revin, V. V., Orekhov, A. N., & Bobryshev, Y. V.
- Affiliations
- Federal Medical Research Centre for Psychiatry and Narcology (RU)
- Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences (RU)
- UNSW Sydney (AU)
- Corresponding author
- Bobryshev, Yuri V.
- Venue
- Immunobiology
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 223
- Issue
- 1
- Pages
- 101-111
- ISSN
- 0171-2985 (ISSN-L)
- OpenAlex
- W2764291671
- Cited by
- 311
- References
- 151
- Citations by year
- 2026: 15 · 2025: 37 · 2024: 29 · 2023: 41 · 2022: 58 · 2021: 48 · 2020: 27 · 2019: 40 · 2018: 16
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Russian Science Foundation (#14-15-00112)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Keywords
- interferon regulatory factors, macrophage polarization, M1 macrophages, M2 macrophages, macrophage differentiation, monocyte differentiation, macrophage heterogeneity, macrophage plasticity, IRF1, IRF5, IRF8, IRF3, IRF4, IRF2, atherosclerosis, tissue microenvironment, wound healing
- MeSH terms
- Animals, Cell Differentiation, Gene Expression Regulation, Humans, Macrophages, Cytokines, Th1 Cells, Th2 Cells, Interferon Regulatory Factors, Cell Transdifferentiation
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
