The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation
Abstract
Although the role of the T(H)1 and T(H)17 subsets of helper T cells as disease mediators in autoimmune neuroinflammation remains a subject of some debate, none of their signature cytokines are essential for disease development. Here we report that interleukin 23 (IL-23) and the transcription factor RORγt drove expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-γ (IFN-γ) and IL-27 acted as negative regulators. Autoreactive helper T cells specifically lacking GM-CSF failed to initiate neuroinflammation despite expression of IL-17A or IFN-γ, whereas GM-CSF secretion by Ifng(-/-)Il17a(-/-) helper T cells was sufficient to induce experimental autoimmune encephalomyelitis (EAE). During the disease effector phase, GM-CSF sustained neuroinflammation via myeloid cells that infiltrated the central nervous system. Thus, in contrast to all other known helper T cell-derived cytokines, GM-CSF serves a nonredundant function in the initiation of autoimmune inflammation regardless of helper T cell polarization.
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
“Th2 cells regulate multiple non-immune tissue cells at mucosal sites”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [25]
In the citing paper
“GM-CSF is essential for the development and progression of EAE. Mice deficient in GM-CSF are resistant to EAE induction, and blockade of GM-CSF in wild-type mice suppresses ongoing disease (McQualter et al., 2001; Codarri et al., 2011).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Codarri et al., 2011
Citations
Cites
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., & Cua, D. J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041257 · Cited by 4,099
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K. P., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00070-4 · Cited by 2,819
IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells
Korn, T., Bettelli, E., Gao, W., Awasthi, A., Jäger, A., Strom, T. B., Oukka, M., & Kuchroo, V. K. (2007) · Nature · doi:10.1038/nature05970 · Cited by 1,896
Aggarwal, S., Ghilardi, N., Xie, M.-H., de Sauvage, F. J., & Gurney, A. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m207577200 · Cited by 1,848
Cited by
Sorted by citations
Items 101–200 of 1,001
Krebs, C. F., Paust, H., Krohn, S., Koyro, T., Brix, S. R., Riedel, J.-H., Bartsch, P., Wiech, T., Meyer‐Schwesinger, C., Huang, J., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.020 · Cited by 218
The Common Cytokine Receptor γ Chain Family of CytokinesPreprint
Lin, J., & Leonard, W. J. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028449 · Cited by 215
“For example, nonpathogenic Th17 cells are generated in the presence of IL-6 and TGF-β (McGeachy et al. 2007), whereas pathogenic Th17 cells are generated when proinflammatory IL-23 is additionally present, thereby inhibiting Th17 cells from producing IL-10 and up-regulating granulocyte macrophage colony-stimulating fa…”
BackgroundInfluentialGut Microbiota, Immunity, and Disease: A Complex Relationship
Kosiewicz, M. M., Zirnheld, A. L., & Alard, P. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00180 · Cited by 207
“Colitis, EAE, and RA are all mediated by IL-17-producing cells, and it is perhaps not surprising that a commensal bacteria that induces Th17 cells may be involved in the etiology of these diseases.”
BackgroundInfluentialRegulation of the T Cell Response by CD39
Takenaka, M. C., Robson, S. C., & Quintana, F. J. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.04.009 · Cited by 211
“GM-CSF, for example, is expressed by pathogenic Th17 cells (74, 75).”
BackgroundCurrent concepts of severe asthma
Ray, A., Raundhal, M. R., Oriss, T. B., Ray, P., & Wenzel, S. E. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84144 · Cited by 208
A basic overview of multiple sclerosis immunopathology
Grigoriadis, N., & Pesch, V. V. (2015) · European Journal of Neurology · doi:10.1111/ene.12798 · Cited by 220
Cytokines IL-17 and IL-22 in the host response to infection
Valeri, M., & Raffatellu, M. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw111 · Cited by 202
“IL-17 receptors work through a pathway that depends on ACT1s (also referred to as CIKS) and activates NF-κB and MAP kinases for the induction of proinflammatory mediators such as IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), some chemokines (CXCL1, CXCL10, CCL2, CCL7, CCL20) and matrix metallo…”
BackgroundSheng, W., Yang, F., Zhou, Y., Yang, H., Low, P. Y., Kemeny, D. M., Tan, P., Moh, A., Kaplan, M. H., Zhang, Y., et al. (2014) · Cell Research · doi:10.1038/cr.2014.154 · Cited by 203
Komuczki, J., Tuzlak, S., Friebel, E., Hartwig, T., Spath, S., Rosenstiel, P., Waisman, A., Opitz, L., Oukka, M., Schreiner, B., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.006 · Cited by 201
Self-citationBrain, O., Owens, B. M. J., Pichulik, T., Allan, P., Khatamzas, E., Leslie, A. J., Steevels, T. A. M., Sharma, S., Mayer, A., Catuneanu, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.035 · Cited by 201
“This included elevated expression of the miR-29-target genes Il23a and Il12b (Figures 6D and 6E), as well as mRNA encoding the key Th17 cytokines IL-17A and GM-CSF (Figures 6F and 6G); both of which are associated with Th17-mediated immunopathology (Griseri et al., 2012; Codarri et al., 2011).”
BackgroundPivotal Roles of GM‐CSF in Autoimmunity and Inflammation
Shiomi, A., & Usui, T. (2015) · Mediators of Inflammation · doi:10.1155/2015/568543 · Cited by 205
Myeloid Colony-Stimulating Factors as Regulators of Macrophage Polarization
Hamilton, T. A., Zhao, C., Pavicic, P. G., & Datta, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00554 · Cited by 200
“Particularly, T-cell derived GM-CSF was recently shown to be critical for disease phenotype in experimental autoimmune encephalomyelitis, generated by IL-23 action on Th17 cells (60, 61).”
BackgroundGriseri, T., McKenzie, B. S., Schiering, C., & Powrie, F. M. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.025 · Cited by 208
Multiple Sclerosis and T Lymphocytes: An Entangled Story
Legroux, L., & Arbour, N. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9614-0 · Cited by 206
“secreted by both myelin specific activated Th1 and Th17 lymphocytes; GM-CSF deficient mice were resistant to the induction of EAE; injection of this cytokine exacerbated disease symptoms whereas administration of blocking antibodies even after disease onset diminished disease severity (McQualter et al. 2001; Codarri e…”
BackgroundIL ‐23: One cytokine in control of autoimmunity
Croxford, A. L., Mair, F., & Becher, B. (2012) · European Journal of Immunology · doi:10.1002/eji.201242598 · Cited by 201
COVID-19 revisiting inflammatory pathways of arthritis
Schett, G., Manger, B., Simon, D., & Caporali, R. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0451-z · Cited by 191
Defining the human T helper 17 cell phenotype
Annunziato, F., Cosmi, L., Liotta, F., Maggi, E., & Romagnani, S. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.05.004 · Cited by 202
Akdiş, M., Palomares, Ó., van de Veen, W., van Splunter, M. E., & Akdiş, C. A. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.05.003 · Cited by 201
T‐cell trafficking in the central nervous system
Sallusto, F., Impellizzieri, D., Basso, C., Laroni, A., Uccelli, A., Lanzavecchia, A., & Engelhardt, B. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01140.x · Cited by 190
“showed that GM-CSF, which is induced in Th17 cells by IL-23, is the critical pathogenetic factor required in the effector phase of EAE (35, 36).”
BackgroundRole of Spleen-Derived Monocytes/Macrophages in Acute Ischemic Brain Injury
Kim, E., Yang, J., Beltran, C., & Cho, S. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.101 · Cited by 188
van Hamburg, J. P., & Tas, S. W. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.12.006 · Cited by 192
Th17 cell pathogenicity and plasticity in rheumatoid arthritis
Yang, P., Qian, F., Zhang, M.-F., Xu, A., Wang, X., Jiang, B., & Zhou, L. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.4ru0619-197r · Cited by 184
Chong, W. P., Mattapallil, M. J., Raychaudhuri, K., Bing, S. J., Wu, S., Zhong, Y., Wang, W., Chen, Z., Silver, P. B., Jittayasothorn, Y., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.022 · Cited by 191
“After centrifugation, the resultant cell pellet was resuspended in RPMI medium containing 1 mg/ml collagenase D and incubated for 45 min at 37 C. Samples were then dispersed by pipetting several times, washed, filtered, and suspended in RPMImediumwith 10%FCS. Brains and spinal cords frommice with EAEwere removed,mince…”
InfluentialIL ‐17: overview and role in oral immunity and microbiome
Abusleme, L., & Moutsopoulos, N. M. (2016) · Oral Diseases · doi:10.1111/odi.12598 · Cited by 189
“Th17 cells in different contexts can also produce other cytokines such as IL-17F, IL-21, IL-22 and granulocytemacrophage colony-stimulating factor (GM-CSF), at varying expression levels (Liang et al., 2006, Korn et al., 2007, Codarri et al., 2011).”
Myeloid cells — targets of medication in multiple sclerosis
Mishra, M. K., & Yong, V. W. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.110 · Cited by 190
The role of transforming growth factor β in T helper 17 differentiation
Zhang, S. (2018) · Immunology · doi:10.1111/imm.12938 · Cited by 194
Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma
Jacquelot, N., Seillet, C., Wang, M., Pizzolla, A., Liao, Y., Hediyeh-zadeh, S., Grisaru‐Tal, S., Louis, C., Huang, Q., Schreuder, J., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00943-z · Cited by 186
Bandukwala, H. S., Gagnon, J. D., Togher, S., Greenbaum, J., Lamperti, E. D., Parr, N. J., Molesworth, A. M. H., Smithers, N. N., Lee, K. C., Witherington, J. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212264109 · Cited by 184
“3E), in concordance with a previous report that demonstrates a role for T-cell–derived GM-CSF in macrophage recruitment (14).”
BackgroundResultHirota, K., Hashimoto, M., Ito, Y., Matsuura, M., Ito, H., Tanaka, M., Watanabe, H., Kondoh, G., Tanaka, A., Yasuda, K., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.009 · Cited by 181
Ichiyama, K., González-Martín, A., Kim, B. S., Jin, H. Y., Jin, W., Xu, W. M., Sabouri-Ghomi, M., Xu, S., Zheng, P., Xiao, C., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.015 · Cited by 185
“Furthermore, two papers have found that granulocyte-macrophage colonystimulating factor (GM-CSF) produced by Th17 cells is a crucial factor for the pathogenicity of Th17 cells during experimental autoimmune encephalomyelitis (EAE) (Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundHou, Y., Zhu, L., Tian, H., Sun, H.-X., Wang, R., Zhang, L., & Zhao, Y. (2018) · Protein & Cell · doi:10.1007/s13238-018-0505-z · Cited by 179
“This article is an open access publication P ro te in & C e ll Il23r and Rorc (encoding RORγ), establishing a positive feedback loop and stabilizing expression of genes encoding pro-inflammatory effector molecules including Il17a, Il17f, Il22 and Csf2 (Parham et al., 2002; Codarri et al., 2011).”
BackgroundGM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis
Galli, E., Hartmann, F. J., Schreiner, B., Ingelfinger, F., Arvaniti, E., Diebold, M., Mrdjen, D., van der Meer, F., Krieg, C., Nimer, F. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0521-4 · Cited by 197
Lin, C., Bradstreet, T. R., Schwarzkopf, E. A., Sim, J. E., Carrero, J. A., Chou, C., Cook, L. E., Egawa, T., Taneja, R., MURPHY, K. M. M., et al. (2014) · Nature Communications · doi:10.1038/ncomms4551 · Cited by 181
Cytokines in Autoimmune Uveitis
Horai, R., & Caspi, R. R. (2011) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2011.0042 · Cited by 181
Modeling the heterogeneity of multiple sclerosis in animals
Simmons, S. B., Pierson, E. R., Lee, S. Y., & Goverman, J. M. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.04.006 · Cited by 184
Mechanisms regulating regional localization of inflammation during CNS autoimmunity
Pierson, E. R., Simmons, S. B., Castelli, L., & Goverman, J. M. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01126.x · Cited by 188
Ditoro, D. F., Harbour, S. N., Bando, J. K., Benavides, G. A., Witte, S. J., Laufer, V. A., Moseley, C. E., Singer, J. R., Frey, B. F., Turner, H., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.03.013 · Cited by 178
Cook, D. N., Kang, H. S., & Jetten, A. M. (2015) · Nuclear Receptor Research · doi:10.11131/2015/101185 · Cited by 181
Modulators of the Nuclear Receptor Retinoic Acid Receptor-Related Orphan Receptor-γ (RORγ or RORc)
Fauber, B. P., & Magnuson, S. R. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401901d · Cited by 171
Ahl, P. J., Hopkins, R. A., Xiang, W. W., Au, B. V., Kaliaperumal, N., Fairhurst, A., & Connolly, J. E. (2020) · Communications Biology · doi:10.1038/s42003-020-1027-9 · Cited by 181
Cutting Edge: The Pathogenicity of IFN-γ–Producing Th17 Cells Is Independent of T-bet
Duhen, R., Glatigny, S., Arbelaez, C. A., Blair, T. C., Oukka, M., & Bettelli, E. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203172 · Cited by 176
Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)
Bengsch, B., Seigel, B., Flecken, T., Wolanski, J., Blum, H. E., & Thimme, R. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103801 · Cited by 171
“Indeed, neutralization of IL-17 was inefficient in avoiding Th17-cell mediated disease (29), and several studies suggest that other cytokines produced by Th17 cells, such as GM-CSF, may be more critically involved in inflammation compared with IL-17 (30, 31).”
BackgroundWang, Z., Yin, W., Zhu, L., Li, J., Yao, Y., Chen, F., Sun, M., Zhang, J., Shen, N., Song, Y., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.05.008 · Cited by 156
Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells
Jain, R., Chen, Y., Kanno, Y., Joyce-Shaikh, B., Vahedi, G., Hirahara, K., Blumenschein, W. M., Sukumar, S., Haines, C. J., Sadekova, S., et al. (2016) · Immunity · doi:10.1016/j.immuni.2015.11.009 · Cited by 167
“Recent findings suggest that IL-23 operates through multiple pathways to generate mature pathogenic Th17 cells including maintenance of Th17 signature genes (Rorc and Il17), induction of effector genes (Il22, Csf2, and Ifng), suppression of repressive factors (Ahr, c-maf), and most importantly by enhancing its own sig…”
InfluentialMultiple sclerosis-associated IL2RA polymorphism controls GM-CSF production in human TH cells
Hartmann, F. J., Khademi, M., Aram, J., Ammann, S., Kockum, I. S., Constantinescu, C. S., Gran, B., Piehl, F., Olsson, T. P., Deak, L. C., et al. (2014) · Nature Communications · doi:10.1038/ncomms6056 · Cited by 186
Induction of regulatory Tr1 cells and inhibition of TH17 cells by IL-27
Pot, C., Apétoh, L., Awasthi, A., & Kuchroo, V. K. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.08.003 · Cited by 175
“Interestingly, IL-27 was also shown to mediate the protective effect of Bone marrow stromal cells (BMSCs) that prevent EAE in mice and suppress IL-17 production [76].”
BackgroundInfluentialEstrogen Receptor-Dependent Regulation of Dendritic Cell Development and Function
Laffont, S., Seillet, C., & Guéry, J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00108 · Cited by 170
“On the other hand, CD4+ T cell-derived Csf-2 production can drive the generation of mo-DC during inflammatory diseases (100, 101) and is essential for the pathogenicity of Th17 cells in CNS autoimmunity (102, 103).”
BackgroundAdvances in the immunopathogenesis of multiple sclerosis
Yadav, S. K., Mindur, J. E., Ito, K., & Dhib-Jalbut, S. S. (2015) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000205 · Cited by 173
Inhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis
Basler, M., Mundt, S., Muchamuel, T., Moll, C., Jiang, J., Groettrup, M., & Kirk, C. J. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303543 · Cited by 163
“Isolation of mononuclear cells from CNS Mice were sacrificed and perfused with cold PBS to minimize contamination of brain and spinal cord with blood-derived leukocytes of peripheral blood.”
BackgroundResultInfluentialChen, K., & Kolls, J. K. (2017) · Gene · doi:10.1016/j.gene.2017.01.016 · Cited by 170
“Recent publications also suggest that GMCSF instead of IL-17A produced by Th17 cells is a critical pathogenic factor in EAE (Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundIL-12-and IL-23 in health and disease
Croxford, A. L., Kulig, P., & Becher, B. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.07.017 · Cited by 160
Multiple sclerosis and the role of immune cells
Høglund, R. A. (2014) · World Journal of Experimental Medicine · doi:10.5493/wjem.v4.i3.27 · Cited by 168
Autoimmunity in Parkinson's Disease: The Role of α-Synuclein-Specific T Cells
Garretti, F., Agalliu, D., Arlehamn, C. S. L., Sette, A., & Sulzer, D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00303 · Cited by 171
The Dopaminergic System in Autoimmune Diseases
Pacheco, R., Contreras, F., & Zouali, M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00117 · Cited by 161
When encephalitogenic T cells collaborate with microglia in multiple sclerosis
Dong, Y., & Yong, V. W. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0253-6 · Cited by 169
Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases
Hamilton, J. A., Cook, A. D., & Tak, P. P. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.231 · Cited by 164
Lin, C., & Edelson, B. T. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700263 · Cited by 164
“development (80, 81), the earlier studies did not provide a”
BackgroundResultInfluentialNovel therapeutic targets in rheumatoid arthritis
Koenders, M. I., & van den Berg, W. B. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.02.001 · Cited by 160
Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases
Chen, M. L., & Sundrud, M. S. (2016) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000714 · Cited by 162
“In mice, Th17-driven EAE (the model of MS) requires GM-CSF, and IL-23 induces GM-CSF expression in Th17 cells.(120) As noted above, Powrie et al reported that IL-23–dependent colitis in mice also involves GM-CSF.”
BackgroundHucke, S., Eschborn, M., Liebmann, M., Herold, M. V. B., Freise, N., Engbers, A., Ehling, P., Meuth, S. G., Roth, J., Kuhlmann, T., et al. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.11.001 · Cited by 161
“As GM-CSF is necessary for EAE induction and targets CNS-infiltrating myeloid cells [10], it could be speculated that during EAE under NaClhigh diet conditions, myeloid cell activation is fueled by the enhanced presence of GM-CSF-producing Th17 cells.”
BackgroundSpath, S., Komuczki, J., Hermann, M., Pelczar, P., Mair, F., Schreiner, B., & Becher, B. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.007 · Cited by 157
Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis
Burmester, G. R., Weinblatt, M. E., McInnes, I. B., Porter, D. R., Барбараш, О. Л., Vatutin, M. T., Szombati, I., Esfandiari, E., Sleeman, M. A., Kane, C. D., et al. (2012) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2012-202450 · Cited by 161
Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-β Therapy
Rasouli, J., Ćirić, B., Imitola, J., GONNELLA, P. A., Hwang, D. H., Mahajan, K. R., Mari, E. R., Safavi, F., Leist, T. P., Zhang, G., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1403243 · Cited by 156
“such as T cells (4, 5) and monocytes/macrophages, or by resident tissue cells (7–10).”
BackgroundTranscription Factor Bhlhe40 in Immunity and Autoimmunity
Cook, M. E., Jarjour, N. N., Lin, C., & Edelson, B. T. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.09.002 · Cited by 148
Nuclear factor kappa B (NF-κB) in multiple sclerosis pathology
Guire, C. M., Prinz, M., Beyaert, R., & Loo, G. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.08.001 · Cited by 160
Parajuli, B., Sonobe, Y., Kawanokuchi, J., Doi, Y., Noda, M., Takeuchi, H., Mizuno, T., & Suzumura, A. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-268 · Cited by 159
“Indeed, GM-CSF-deficient mice are reportedly resistant to experimental autoimmune encephalomyelitis, an animal model of MS [16,17], in which microglial activation is reduced.”
BackgroundVaccines for Pseudomonas aeruginosa : a long and winding road
Priebe, G. P., & Goldberg, J. B. (2014) · Expert Review of Vaccines · doi:10.1586/14760584.2014.890053 · Cited by 158
“DC: Dendritic cell; LPS: Lipopolysaccharide; MHC: Major histocompatibility complex; PMN: Polymorphonuclear leukocyte; TTSS: Type III secretion system. informahealthcare.com 513 and GM-CSF secretion (live-attenuated vaccines), which will act in concert with opsonophagocytic antibodies to enhance bacterial clearance.”
BackgroundInfluentialMeierovics, A. I., & Cowley, S. C. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160637 · Cited by 149
Inflammasome activation in multiple sclerosis and experimental autoimmune encephalomyelitis ( EAE )
Barclay, W., & Shinohara, M. L. (2016) · Brain Pathology · doi:10.1111/bpa.12477 · Cited by 154
Lévesque, S. A., Paré, A., Mailhot, B., Bellver‐Landete, V., Kébir, H., Lécuyer, M., Alvarez, J. I., Prat, A., Vaccari, J. P. D. R., Keane, R. W., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151437 · Cited by 151
“…was found to prevent or alleviate EAE symptoms, as demonstrated by the following studies: GM-CSF (McQualter et al., 2001; Kroenke et al., 2008, 2010; Codarri et al., 2011; El-Behi et al., 2011), IL-6 (Eugster et al., 1998; Okuda et al., 1998; Samoilova et al., 1998), Ccl2 (Huang et al., 2001),…”
BackgroundInfluentialEnvironmental factors in autoimmune diseases and their role in multiple sclerosis
Haase, S., Grohme, D. A., Erzler, M., Binsfeld, M., Haghikia, A., Müller, D. N., Linker, R. A., & Kleinewietfeld, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2311-1 · Cited by 156
“More recent studies found that the pathogenicity of Th17 cells additionally depends on the IL-23-induced production of the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), probably explaining the incomplete protection from EAE in IL-17-deficient mice [47, 48].”
Backgrounddos Passos, G. R., Sato, D. K., Becker, J., & Fujihara, K. (2016) · Mediators of Inflammation · doi:10.1155/2016/5314541 · Cited by 155
“…fail to control or even increase disease activity in NMOSD [4], thus suggesting a distinct underlying pathophysiological process in each of those disorders and highlighting the need for a precise distinction between them in order to avoid the potentially harmful consequences of a misdiagnosis.”
BackgroundT-Cell-Driven Inflammation as a Mediator of the Gut-Brain Axis Involved in Parkinson's Disease
Campos‐Acuña, J., Elgueta, D., & Pacheco, R. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00239 · Cited by 150
Amorim, A., De Feo, D., Friebel, E., Ingelfinger, F., Anderfuhren, C. D., Krishnarajah, S., Andreadou, M., Welsh, C. A., Liu, Z., Ginhoux, F., et al. (2022) · Nature Immunology · doi:10.1038/s41590-021-01117-7 · Cited by 140
Larochelle, C., Cayrol, R., Kebir, H., Alvarez, J. I., Lécuyer, M.-A., Ifergan, I., Viel, É., Bourbonnière, L., Beauseigle, D., Terouz, S., et al. (2012) · Brain · doi:10.1093/brain/aws212 · Cited by 145
“More recently, IL23, in part through ROR- , was shown to drive the production of GM–CSF, an essential factor for EAE induction (Ponomarev et al., 2007; Kroenke et al., 2010; Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundLiu, S.-Q., Jiang, S., Li, C., Zhang, B., & Li, Q.-J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.550723 · Cited by 145
“However, a closer examination at the effector function of these CD4 T cells revealed that KO cells collected from the spinal cords and spleens of EAE mice had significantly diminished IL-17 expression (Fig.”
BackgroundInfluentialTh1/Th2/Th17/Treg cytokines in Guillain–Barré syndrome and experimental autoimmune neuritis
Zhang, H., Zheng, X., & Zhu, J. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.05.005 · Cited by 143
TH17 cytokines in autoimmune neuro-inflammation
Becher, B., & Segal, B. M. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.08.005 · Cited by 147
Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases
Abraham, C., Dulai, P. S., Vermeire, S., & Sandborn, W. J. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.10.018 · Cited by 142
Bystander CD4+ T cells: crossroads between innate and adaptive immunity
Lee, H., Cho, M.-J., & Choi, J. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00486-7 · Cited by 157
GM-CSF: A Promising Target in Inflammation and Autoimmunity
Lee, M.-C., Achuthan, A. A., & Hamilton, J. A. (2020) · ImmunoTargets and Therapy · doi:10.2147/itt.s262566 · Cited by 157
IL-17+ CD8+ T cells: Differentiation, phenotype and role in inflammatory disease
Srenathan, U., Steel, K. J. A., & Taams, L. S. (2016) · Immunology Letters · doi:10.1016/j.imlet.2016.05.001 · Cited by 143
Emerging role of IL-17 and Th17 cells in systemic lupus erythematosus
Martin, J. C., Baeten, D., & Josien, R. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.05.004 · Cited by 144
Al‐Mossawi, H., Chen, L., Fang, H., Ridley, A., de Wit, J., Yager, N., Hammitzsch, A., Pulyakhina, I., Fairfax, B. P., Simone, D., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01771-2 · Cited by 142
Natalizumab in Multiple Sclerosis Treatment: From Biological Effects to Immune Monitoring
Khoy, K., Mariotte, D., Defer, G. L., Petit, G., Toutirais, O., & Mauff, B. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.549842 · Cited by 140
GM-CSF-Dependent Inflammatory Pathways
Hamilton, J. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02055 · Cited by 146
CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells
Kara, E. E., McKenzie, D. R., Bastow, C. R., Gregor, C. E., Fenix, K. A., Ogunniyi, A. D., Paton, J. C., Mack, M., Pombal, D. R., Seillet, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms9644 · Cited by 136
Arnold, I. C., Hitzler, I., & Mueller, A. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00010 · Cited by 140
“…CNS inflammation based on the evidence that autoreactive helper T-cells specifically lacking GM–CSF failed to initiate neuro-inflammation despite expression of IL-17A and IFN-γ, whereas GM–CSF secretion by Ifng −/−Il17a−/− helper T-cells was sufficient to induce EAE (Codarri et al., 2011).”
Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies
Bonaventura, A., Vecchié, A., Wang, T. S., Lee, E., Cremer, P. C., Carey, B. C., Rajendram, P., Hudock, K. M., Korbee, L. L., Tassell, B. W. V., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01625 · Cited by 137
Luchtman, D. W., Ellwardt, E., Larochelle, C., & Zipp, F. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.07.013 · Cited by 137
Human and Mouse Mononuclear Phagocyte Networks: A Tale of Two Species?
Reynolds, G., & Haniffa, M. A. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00330 · Cited by 138
“Nevertheless, there are functional differences in lymphocytes between the two species, such as differentiation requirements for IL-17 (36) and GM-CSF (37, 38) secreting CD4+ T cells, the specificity of granzyme and FOXP3 expression to define natural Tregs (39), the distinct classes of immunoglobulin (40) and human CD1…”
BackgroundT Helper Lymphocyte Subsets and Plasticity in Autoimmunity and Cancer: An Overview
Ivanova, E. A., & Orekhov, A. N. (2015) · BioMed Research International · doi:10.1155/2015/327470 · Cited by 145
“Moreover, GM-CSF has also been demonstrated to participate in the pathological process [113, 114] and elevated levels of IL-17 were found to be associated with the disease [115], pointing to an important role of Th17 cells in the MS pathogenesis, which has been also confirmed by a number of recent…”
BackgroundDuhen, T. M., & Campbell, D. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302734 · Cited by 135
A Close Encounter of the Third Kind
Mildner, A., Yona, S., & Jung, S. (2013) · Advances in immunology · doi:10.1016/b978-0-12-417028-5.00003-x · Cited by 136
Wong, H., & Hoeffer, C. A. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.010 · Cited by 131
“Interestingly, Th17 cells can themselves secrete IL-6 (Langrish et al., 2005), which can result in a positive feedback loop, as well as GM-CSF (Codarri et al., 2011) and TNFα (Langrish et al., 2005), which can synergize with IL-17A to enhance the inflammatory response.”
BackgroundLiu, X., Li, H., Zhong, B., Blonska, M., Gorjestani, S., Yan, M., Tian, Q., Zhang, D., Lin, X., & Dong, C. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20122327 · Cited by 130
Th17 and Cognitive Impairment: Possible Mechanisms of Action
Cipollini, V., Anrather, J., Orzi, F., & Iadecola, C. (2019) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2019.00095 · Cited by 133
“Unlike other cytokines, GM-CSF has a nonredundant role in promoting EAE and its secretion is able alone to render MOG-specific T cells autoaggressive and pathogenic (Codarri et al., 2011).”
BackgroundT lymphocytes in the intestinal mucosa: defense and tolerance
Ma, H., Tao, W., & Zhu, S. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0208-2 · Cited by 125
Suryawanshi, A. S., Manoharan, I., Hong, Y., Swafford, D., Majumdar, T., Taketo, M. M., Manicassamy, B., Koni, P. A., Thangaraju, M., Sun, Z., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402691 · Cited by 127
GM-CSF in Neuroinflammation: Licensing Myeloid Cells for Tissue Damage
Croxford, A. L., Spath, S., & Becher, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.004 · Cited by 132
Metadata
- Authors
- Codarri, L., Gyülvészi, G., Tosevski, V., Hesske, L., Fontana, A., Magnenat, L., Suter, T., & Becher, B.
- Affiliations
- University Hospital Zurich (CH)
- University of Zurich (CH)
- Merck Serono S.A. (Switzerland) (CH)
- Corresponding author
- Becher, Burkhard
- Venue
- Nature Immunology
- Published
- 2011-04-24
- Volume
- 12
- Issue
- 6
- Pages
- 560-567
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2157837362
- Cited by
- 1,191
- References
- 44
- Citations by year
- 2026: 31 · 2025: 48 · 2024: 60 · 2023: 53 · 2022: 61 · 2021: 73 · 2020: 85 · 2019: 83 · 2018: 72 · 2017: 99 · 2016: 96 · 2015: 117 · 2014: 103 · 2013: 98 · 2012: 82
- FWCI
- 70.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- RORγt, GM-CSF, experimental autoimmune encephalomyelitis, T helper cells, IL-23, autoimmune neuroinflammation, Th1 cells, Th17 cells, myeloid cell infiltration, IL-12, interferon-gamma, IL-27, cytokine regulation
- MeSH terms
- Animals, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Female, Flow Cytometry, Glycoproteins, T-Lymphocytes, Helper-Inducer, Interferon-gamma, Interleukins, Male, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Peptide Fragments, Granulocyte-Macrophage Colony-Stimulating Factor, Mice, Knockout, Th1 Cells, Interleukin-12, Interleukin-17, Mice, Interleukin-23, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, Myelin-Oligodendrocyte Glycoprotein
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
