Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity
Open accessAbstract
Sex differences in multiple sclerosis (MS) incidence and severity have long been recognized. However, the underlying cellular and molecular mechanisms for why male sex is associated with more aggressive disease remain poorly defined. Using a T cell adoptive transfer model of chronic experimental autoimmune encephalomyelitis (EAE), we find that male Th17 cells induce disease of increased severity relative to female Th17 cells, irrespective of whether transferred to male or female recipients. Throughout the disease course, a greater frequency of male Th17 cells produce IFNγ, a hallmark of pathogenic Th17 responses. Intriguingly, XY chromosomal complement increases the pathogenicity of male Th17 cells. An X-linked immune regulator, Jarid1c, is downregulated in pathogenic male murine Th17 cells, and functional experiments reveal that it represses the severity of Th17-mediated EAE. Furthermore, Jarid1c expression is downregulated in CD4 + T cells from MS-affected individuals. Our data indicate that male sex chromosomal complement critically regulates Th17 cell pathogenicity.
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Dysregulation of microglial functions is associated with several health concerns that often show sex prevalences, including Alzheimer's disease (more prevalent among females), Parkinson's disease (more male-prevalent), and various other neurodevelopmental, neuropsychiatric and neurodegenerative disorders.
“Dysregulation of microglial functions is associated with several health concerns that often show sex prevalences, not only affecting Alzheimer’s disease, which shows more prevalence among females, and Parkinson’s disease, more male-prevalent, but also including various other neurodevelopmental, neuropsychiatric and neurodegenerative disorders [38–43].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [43]
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · see citing works
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 · see citing works
A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment
Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., & Glimcher, L. H. (2000) · Cell · doi:10.1016/s0092-8674(00)80702-3 · Cited by 3,589 · see citing works
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452 · see citing works
A role for Wnt signalling in self-renewal of haematopoietic stem cells
Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L. (2003) · Nature · doi:10.1038/nature01593 · Cited by 2,159 · see citing works
Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity
Browne, P., Chandraratna, D., Angood, C., Tremlett, H., Baker, C., Taylor, B. V., & Thompson, A. J. (2014) · Neurology · doi:10.1212/wnl.0000000000000768 · Cited by 1,223 · see citing works
Fate mapping of IL-17-producing T cells in inflammatory responses
Hirota, K., Duarte, J. H., Veldhoen, M., Hornsby, E., Li, Y., Cua, D. J., Ahlfors, H., Wilhelm, C., Tolaini, M., Menzel, U., et al. (2011) · Nature Immunology · doi:10.1038/ni.1993 · Cited by 1,176 · see citing works
Induction and molecular signature of pathogenic TH17 cells
Lee, Y., Awasthi, A., Yosef, N., Quintana, F. J., Xiao, S., Peters, A., Wu, C., Kleinewietfeld, M., Kunder, S., Hafler, D. A., et al. (2012) · Nature Immunology · doi:10.1038/ni.2416 · Cited by 1,174 · see citing works
Late Developmental Plasticity in the T Helper 17 Lineage
Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.005 · Cited by 1,053 · see citing works
Jäger, A., Dardalhon, V., Sobel, R. A., Bettelli, E., & Kuchroo, V. K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901906 · Cited by 783 · see citing works
The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses
Naviaux, R. K., Costanzi, E., Haas, M., & Verma, I. M. (1996) · Journal of Virology · doi:10.1128/jvi.70.8.5701-5705.1996 · Cited by 735 · see citing works
TLR7 escapes X chromosome inactivation in immune cells
Souyris, M., Cénac, C., Azar, P., Daviaud, D., Canivet, A., Grunenwald, S., Pienkowski, C., Chaumeil, J., Mejía, J. E., & Guéry, J. (2018) · Science Immunology · doi:10.1126/sciimmunol.aap8855 · Cited by 650 · see citing works
Sabatos, C. A., Chakravarti, S., Cha, E., Schubart, A., Fueyo, A. S., Zheng, X. X., Coyle, A. J., Strom, T. B., Freeman, G. J., & Kuchroo, V. K. (2003) · Nature Immunology · doi:10.1038/ni988 · Cited by 629 · see citing works
GM-CSF: From Growth Factor to Central Mediator of Tissue Inflammation
Becher, B., Tugues, S., & Greter, M. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.026 · Cited by 593 · see citing works
Arnold, A. P., & Chen, X. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2008.11.001 · Cited by 587 · see citing works
Genetic Control of Autoimmune Diabetes in the Nod Mouse
Wicker, L. S., Todd, J. A., & Peterson, L. B. (1995) · Annual Review of Immunology · doi:10.1146/annurev.iy.13.040195.001143 · Cited by 582 · see citing works
Single-cell genomics unveils critical regulators of Th17 cell pathogenicity
Gaublomme, J. T., Yosef, N., Lee, Y., Gertner, R. S., Yang, L. V., Wu, C., Pandolfi, P. P., Mak, T., Satija, R., Shalek, A. K., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.009 · Cited by 575 · see citing works
Bending, D., Peña, H. D. L., Veldhoen, M., Phillips, J. M., Uyttenhove, C., Stockinger, B., & Cooke, A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37865 · Cited by 559 · see citing works
Preferential recruitment of interferon‐γ–expressing T <sub>H</sub> 17 cells in multiple sclerosis
Kebir, H., Ifergan, I., Alvarez, J. I., Bernard, M., Poirier, J., Arbour, N., Duquette, P., & Prat, A. (2009) · Annals of Neurology · doi:10.1002/ana.21748 · Cited by 551 · see citing works
McKenzie, B., Mamik, M. K., Saito, L. B., Boghozian, R., Monaco, M. C., Major, E. O., Lu, J., Branton, W. G., & Power, C. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722041115 · Cited by 515 · see citing works
McRae, B. L., Vanderlugt, C. L., Canto, M. C. D., & Miller, S. D. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.1.75 · Cited by 512 · see citing works
Effector T cell plasticity: flexibility in the face of changing circumstances
Murphy, K. M., & Stockinger, B. (2010) · Nature Immunology · doi:10.1038/ni.1899 · Cited by 482 · see citing works
Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation
Mayo, L., Trauger, S. A., Blain, M., Nadeau, M., Patel, B., Alvarez, J. I., Mascanfroni, I. D., Yeste, A., Kivisäkk, P., Kallas, K., et al. (2014) · Nature Medicine · doi:10.1038/nm.3681 · Cited by 472 · see citing works
Th17 cells are long lived and retain a stem cell-like molecular signature
Muranski, P., Borman, Z. A., Kerkar, S. P., Klebanoff, C. A., Ji, Y., Sanchez-Perez, L., Sukumar, M., Reger, R. N., Yu, Z., Kern, S. J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.019 · Cited by 443 · see citing works
Christianson, S. W., Shultz, L. D., & Leiter, E. H. (1993) · Diabetes · doi:10.2337/diab.42.1.44 · Cited by 427 · see citing works
A role for sex chromosome complement in the female bias in autoimmune disease
Smith-Bouvier, D. L., Divekar, A., Manda, S. V., Du, S., Tiwari-Woodruff, S. K., King, J. K., Arnold, A. P., Singh, R. R., & Voskuhl, R. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20070850 · Cited by 398 · see citing works
Rangachari, M., Zhu, C., Sakuishi, K., Xiao, S., Karman, J., Chen, A., Angin, M., Wakeham, A., Greenfield, E. A., Sobel, R. A., et al. (2012) · Nature Medicine · doi:10.1038/nm.2871 · Cited by 394 · see citing works
Self-citationEssentials of Th17 cell commitment and plasticity
Muranski, P. J., & Restifo, N. P. (2013) · Blood · doi:10.1182/blood-2012-09-378653 · Cited by 386 · see citing works
T‐helper 17 cells expand in multiple sclerosis and are inhibited by interferon‐β
Durelli, L., Conti, L., Clerico, M., Boselli, D., Contessa, G., Ripellino, P., Ferrero, B., Eid, P., & Novelli, F. (2009) · Annals of Neurology · doi:10.1002/ana.21652 · Cited by 374 · see citing works
Martín‐Orozco, N., Chung, Y., Chang, S. H., Wang, Y., & Dong, C. (2009) · European Journal of Immunology · doi:10.1002/eji.200838475 · Cited by 359 · see citing works
Disability progression in multiple sclerosis is slower than previously reported
Tremlett, H. L., Paty, D. W., & Devonshire, V. A. (2006) · Neurology · doi:10.1212/01.wnl.0000194259.90286.fe · Cited by 345 · see citing works
The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice
Chen, X., McClusky, R., Chen, J., Beaven, S. W., Tontonoz, P., Arnold, A. P., & Reue, K. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002709 · Cited by 326 · see citing works
Escape from X Inactivation Varies in Mouse Tissues
Berletch, J. B., Ma, W., Yang, F., Shendure, J., Noble, W. S., Distèche, C. M., & Deng, X. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005079 · Cited by 292 · see citing works
Inoue, M., Williams, K. L., Gunn, M. D., & Shinohara, M. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201836109 · Cited by 288 · see citing works
Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice
Gatewood, J. D., Wills, A., Shetty, S. R. J., Xu, J., Arnold, A. P., Burgoyne, P. S., & Rissman, E. F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3743-05.2006 · Cited by 247 · see citing works
Christensen, J. R., Börnsen, L. S., Ratzer, R. L., Piehl, F., Khademi, M., Olsson, T. P., Sørensen, P. S., & Sellebjerg, F. T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057820 · Cited by 240 · see citing works
Neuroprotection mediated through estrogen receptor-α in astrocytes
Spence, R. D., Hamby, M. E., Umeda, E. A., Itoh, N., Du, S., Wisdom, A. J., Cao, Y., Bondar, G., Lam, J., Ao, Y., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103833108 · Cited by 236 · see citing works
Zhang, M. A., Rego, D., Moshkova, M., Kébir, H., Chruscinski, A. J., Nguyen, H. T., Akkermann, R., Stanczyk, F. Z., Prat, A., Steinman, L., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118458109 · Cited by 216 · see citing works
Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity
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., et al. (2019) · Nature · doi:10.1038/s41586-018-0806-7 · Cited by 215 · see citing works
McCarthy, D. P., Richards, M. H., & Miller, S. D. (2012) · Methods in molecular biology · doi:10.1007/978-1-60761-720-4_19 · Cited by 209 · see citing works
Genetic and hormonal factors in female-biased autoimmunity
Rubtsov, A. V., Rubtsova, K., Kappler, J. W., & Marrack, P. (2010) · Autoimmunity Reviews · doi:10.1016/j.autrev.2010.02.008 · Cited by 207 · see citing works
Farez, M., Quintana, F., Gandhi, R., Izquierdo, G., Lucas, M., & Weiner, H. (2009) · Nature Immunology · doi:10.1038/ni.1775 · Cited by 207 · see citing works
Li, S., Wu, Y., Yang, D., Wu, C., Ma, C., Liu, X., Moynagh, P. N., Wang, B., Hu, G., & Yang, S. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190377 · Cited by 188 · see citing works
Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis
Gracey, E., Yao, Y., Green, B., Qaiyum, Z., Baglaenko, Y., Lin, A., Anton, A., Ayearst, R., Yip, P. S. F., & Inman, R. D. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39464 · Cited by 185 · see citing works
The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity
Itoh, Y., Golden, L. C., Itoh, N., Matsukawa, M. A., Ren, E., Tse, V., Arnold, A. P., & Voskuhl, R. R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126250 · Cited by 181 · see citing works
Reiley, W. W., Shafiani, S., Wittmer, S. T., Tucker-Heard, G., Moon, J. J., Jenkins, M. K., Urdahl, K. B., Winslow, G. M., & Woodland, D. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006298107 · Cited by 179 · see citing works
A Yin-Yang Effect between Sex Chromosome Complement and Sex Hormones on the Immune Response
Palaszynski, K. M., Smith, D. L., Kamrava, S., Burgoyne, P. S., Arnold, A. P., & Voskuhl, R. R. (2005) · Endocrinology · doi:10.1210/en.2005-0284 · Cited by 163 · see citing works
Role of gender in multiple sclerosis: Clinical effects and potential molecular mechanisms
Greer, J. M., & McCombe, P. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.03.003 · Cited by 161 · see citing works
T cell–intrinsic ASC critically promotes TH17-mediated experimental autoimmune encephalomyelitis
Martin, B. N., Wang, C., Zhang, C.-J., Kang, Z., Gulen, M. F., Zepp, J. A., Zhao, J., Bian, G., Do, J., Min, B., et al. (2016) · Nature Immunology · doi:10.1038/ni.3389 · Cited by 154 · see citing works
Sex differences in experimental autoimmune encephalomyelitis in multiple murine strains
Papenfuss, T. L., Rogers, C. J., Gienapp, I., Yurrita, M., McClain, M., Damico, N., Valo, J., Song, F., & Whitacre, C. C. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.01.018 · Cited by 152 · see citing works
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 150 · see citing works
Berard, J. L., Wolak, K., Fournier, S., & David, S. (2010) · Glia · doi:10.1002/glia.20935 · Cited by 147 · see citing works
Genetic proof for the transient nature of the Th17 phenotype
Kurschus, F. C., Croxford, A. L., Heinen, A. P., Wörtge, S., Ielo, D., & Waisman, A. (2010) · European Journal of Immunology · doi:10.1002/eji.201040755 · Cited by 141 · see citing works
Outchkourov, N. S., Muiño, J. M., Kaufmann, K., van IJcken, W. F. J., Koerkamp, M. J. A. G., van Leenen, D., de Graaf, P., Holstege, F. C. P., Grosveld, F. G., & Timmers, H. T. M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.02.030 · Cited by 136 · see citing works
QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2
Encinas, J. A., Wicker, L. S., Peterson, L. B., Mukasa, A., Teuscher, C., Sobel, R. A., Weiner, H. L., Seidman, C. E., Seidman, J. G., & Kuchroo, V. K. (1999) · Nature Genetics · doi:10.1038/5941 · Cited by 131 · see citing works
Du, S., Itoh, N., Askarinam, S., Hill, H., Arnold, A. P., & Voskuhl, R. R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307091111 · Cited by 131 · see citing works
Mayo, L., da Cunha, A. P., Madi, A., Beynon, V., Yang, Z., Alvarez, J. I., Prat, A., Sobel, R. A., Kobzik, L., Lassmann, H., et al. (2016) · Brain · doi:10.1093/brain/aww113 · Cited by 116 · see citing works
Self-citationThe importance of having two X chromosomes
Arnold, A. P., Reue, K., Eghbali, M., Vilain, E., Chen, X., Ghahramani, N., Itoh, Y., Li, J., Link, J. C., Ngun, T., et al. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0113 · Cited by 114 · see citing works
Liu, X., Hoft, D. F., & Peng, G. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133679 · Cited by 113 · see citing works
TGF‐β converts Th1 cells into Th17 cells through stimulation of Runx1 expression
Liu, H., Cao, A., Feng, T., Li, Q., Zhang, W., Yao, S., Dann, S. M., Elson, C. O., & Cong, Y. (2015) · European Journal of Immunology · doi:10.1002/eji.201444726 · Cited by 104 · see citing works
Evidence that the Y chromosome influences autoimmune disease in male and female mice
Teuscher, C., Noubade, R., Spach, K. M., McElvany, B. D., Bunn, J. Y., Fillmore, P. D., Zachary, J. F., & Blankenhorn, E. P. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600536103 · Cited by 100 · see citing works
Secondary Progression in Multiple Sclerosis: Neuronal Exhaustion or Distinct Pathology?
Larochelle, C., Uphaus, T., Prat, A., & Zipp, F. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.02.001 · Cited by 99 · see citing works
Suryani, S., & Sutton, I. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.023 · Cited by 92 · see citing works
Inflammasome Activation by Cystine Crystals
Prencipe, G., Caiello, I., Cherqui, S., Whisenant, T. C., Petrini, S., Emma, F., & Benedetti, F. D. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013060653 · Cited by 92 · see citing works
Sex Differences in Cognitive Impairment in Multiple Sclerosis
Beatty, W. W., & Aupperle, R. L. (2002) · The Clinical Neuropsychologist · doi:10.1076/clin.16.4.472.13904 · Cited by 90 · see citing works
Characterising aggressive multiple sclerosis
Menon, S., Shirani, A., Zhao, Y., Oger, J., Traboulsee, A. L., Freedman, M. S., & Tremlett, H. L. (2013) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-304951 · Cited by 90 · see citing works
Characterization of mouse CD4 T cell subsets defined by expression of KLRG1
Beyersdorf, N., Ding, X., Tietze, J. K., & Hanke, T. (2007) · European Journal of Immunology · doi:10.1002/eji.200737126 · Cited by 81 · see citing works
The Yaa Gene Model of Systemic Lupus Erythematosus
Izui, S., IWAMOTO, M., FOSSATI, U., Merino, R., Takahashi, S., & Ibnou-Zekri, N. (1995) · Immunological Reviews · doi:10.1111/j.1600-065x.1995.tb00068.x · Cited by 81 · see citing works
Rohane, P., Shimada, A., Kim, D. T., Taylor-Edwards, C., Charlton, B., Shultz, L. D., & Fathman, C. G. (1995) · Diabetes · doi:10.2337/diab.44.5.550 · Cited by 77 · see citing works
T-helper cell diversity in experimental autoimmune encephalomyelitis and Multiple Sclerosis
Carbajal, K. S., Mironova, Y. A., Ulrich-Lewis, J. T., Kulkarni, D., Grifka-Walk, H. M., Huber, A. K., Shrager, P., Giger, R., & Segal, B. (2015) · Journal of Immunology · doi:10.4049/jimmunol.1501097 · Cited by 72 · see citing works
Spach, K. M., Blake, M., Bunn, J. Y., McElvany, B. D., Noubade, R., Blankenhorn, E. P., & Teuscher, C. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803200 · Cited by 71 · see citing works
Araújo, L. P., Maricato, J. T., Guereschi, M. G., Takenaka, M. C., Nascimento, V. M., de Melo, F. M., Quintana, F. J., Brum, P. C., & Basso, A. S. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.042 · Cited by 70 · see citing works
Dysregulation of the IL-23/IL-17 axis and myeloid factors in secondary progressive MS
Huber, A. K., Wang, L., Han, P., Zhang, X., EKHOLM, S. E., Srinivasan, A., Irani, D. N., & Segal, B. M. (2014) · Neurology · doi:10.1212/wnl.0000000000000908 · Cited by 69 · see citing works
A Transgenic Model of Central Nervous System Autoimmunity Mediated by CD4+ and CD8+ T and B Cells
Anderson, A. C., Chandwaskar, R., Lee, D. H., Sullivan, J. M., Solomon, A., Rodriguez‐Manzanet, R., Greve, B., Sobel, R. A., & Kuchroo, V. K. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102186 · Cited by 68 · see citing works
Self-citationAbromson‐Leeman, S. R., Bronson, R. T., & Dorf, M. E. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.07.007 · Cited by 65 · see citing works
From a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors
Liang, J., Labadie, S. S., Zhang, B., Ortwine, D. F., Patel, S. D., Vinogradova, M. V., Kiefer, J. R., Mauer, T., Gehling, V. S., Harmange, J.-C., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.05.016 · Cited by 58 · see citing works
A Quantitative Analysis of Suspected Environmental Causes of MS
Sloka, S., Silva, C., Pryse-Phillips, W. E. M., Patten, S. B., Metz, L. M., & Yong, V. W. (2011) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100011124 · Cited by 58 · see citing works
Distinct Th17 inductions contribute to the gender bias in CVB3-induced myocarditis
Li, Z., Yue, Y., & Xiong, S. (2013) · Cardiovascular Pathology · doi:10.1016/j.carpath.2013.02.004 · Cited by 52 · see citing works
Sex-Based Differences in Multiple Sclerosis (Part I): Biology of Disease Incidence
Dunn, S. E., Lee, H., Pavri, F. R., & Zhang, M. A. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_371 · Cited by 47 · see citing works
Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells
Myers, D. R., Norlin, E., Vercoulen, Y., & Roose, J. P. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.037 · Cited by 42 · see citing works
Interleukin-15 plays an essential role in the pathogenesis of autoimmune diabetes in the NOD mouse
Bobbala, D., Chen, X.-L., LeBlanc, C., Mayhue, M., Staňková, J., Tanaka, T. T., Chen, Y.-G., Ilangumaran, S., & Ramanathan, S. (2012) · Diabetologia · doi:10.1007/s00125-012-2675-1 · Cited by 42 · see citing works
Case, L. K., Wall, E. H., Osmanski, E., Dragon, J. A., Saligrama, N., Zachary, J. F., Lemos, B., Blankenhorn, E. P., & Teuscher, C. (2015) · Genome biology · doi:10.1186/s13059-015-0591-7 · Cited by 39 · see citing works
Neuropathological Techniques to Investigate Central Nervous System Sections in Multiple Sclerosis
Bauer, J., & Lassmann, H. (2014) · Methods in molecular biology · doi:10.1007/7651_2014_151 · Cited by 38 · see citing works
Self-citationAxtner, J., & Sommer, S. (2009) · BMC Research Notes · doi:10.1186/1756-0500-2-264 · Cited by 38 · see citing works
Boukhaled, G. M., Cordeiro, B., Deblois, G., Dimitrov, V., Bailey, S. D., Holowka, T., Domi, A., Guak, H., Chiu, H.-H. C., Everts, B., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.026 · Cited by 36 · see citing works
Interferon-β Suppresses Murine Th1 Cell Function in the Absence of Antigen-Presenting Cells
Boivin, N., Baillargeon, J., Doss, P. M. I. A., Roy, A.-P., & Rangachari, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124802 · Cited by 36 · see citing works
Self-citationModelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain
Dang, P. T., Bui, Q., D’Souza, C. S., & Orian, J. M. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2015_378 · Cited by 35 · see citing works
Dasilva, A. G., Liaw, L., & Yong, W. V. (2010) · American Journal of Pathology · doi:10.2353/ajpath.2010.091081 · Cited by 33 · see citing works
Trans-presentation of IL-15 modulates STAT5 activation and Bcl-6 expression in TH1 cells
Cooley, I. D., Read, K. A., & Oestreich, K. J. (2015) · Scientific Reports · doi:10.1038/srep15722 · Cited by 30 · see citing works
Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells
Zhou, X., Dong, T., Fan, Z., Peng, Y., Zhou, R., Wang, X., Song, N., Han, M., Fan, B., Jia, J., et al. (2017) · Scientific Reports · doi:10.1038/srep45468 · Cited by 29 · see citing works
The prevalence of Th17 cells in patients with dilated cardiomyopathy
Yi, A., Jian, L., Hu, X., & Hui, X. (2009) · Clinical and investigative medicine · doi:10.25011/cim.v32i2.6032 · Cited by 20 · see citing works
Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord
Oji, S., Nicolussi, E.-M., Kaufmann, N. C., Zeka, B., Schanda, K., Fujihara, K., Illés, Z., Dahle, C., Reindl, M., Lassmann, H., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151244 · Cited by 17 · see citing works
Self-citationJane‐wit, D., Altuntas, C. Z., Monti, J., Johnson, J. M., Forsthuber, T. G., & Tuohy, V. K. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2008.070324 · Cited by 11 · see citing works
Hummel, S., Wilms, D., Vitacolonna, M., & Zöller, M. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.5.898 · Cited by 11 · see citing works
Dhaeze, T., Lachance, C., Tremblay, L., Grasmuck, C., Bourbonnière, L., Larouche, S., Saint‐Laurent, O., Lécuyer, M., Rébillard, R., Zandee, S., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.124885 · Cited by 9 · see citing works
Yeola, A. P., Doss, P. M. I. A., Baillargeon, J., Akbar, I., Mailhot, B., Balood, M., Talbot, S., Anderson, A. C., Lacroix, S., & Rangachari, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03115 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
1 of the 98 references couldn’t be matched to a known paper.
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Potential biological contributers to the sex difference in multiple sclerosis progression
Álvarez‐Sánchez, N., & Dunn, S. E. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1175874 · Cited by 71 · see citing works
Histone demethylases in the regulation of immunity and inflammation
Qu, L., Yin, T., Zhao, Y., Lv, W., Liu, Z., Chen, C., Liu, K., Shan, S., Zhou, R., Li, X., et al. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01489-9 · Cited by 63 · see citing works
X chromosome agents of sexual differentiation
Arnold, A. P. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00697-0 · Cited by 59 · see citing works
Charabati, M., Grasmuck, C., Ghannam, S., Bourbonnière, L., Fournier, A. P., Lécuyer, M., Tastet, O., Kébir, H., Rébillard, R., Hoornaert, C., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abj0473 · Cited by 51 · see citing works
The X factor in neurodegeneration
Voskuhl, R. R., & Itoh, Y. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211488 · Cited by 34 · see citing works
Liu, H., Zhai, L., Liu, Y., Lü, D., Ark, A. V., Yang, T., & Krawczyk, C. M. (2023) · Science Advances · doi:10.1126/sciadv.adg0731 · Cited by 29 · see citing works
Ocañas, S. R., Ansere, V. A., Tooley, K. B., Hadad, N., Chucair‐Elliott, A. J., Stanford, D. R., Rice, S., Wronowski, B., Pham, K. D., Hoffman, J. M., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02860-0 · Cited by 25 · see citing works
Muefong, C. N., Owolabi, O., Donkor, S. A., Charalambous, S., Mendy, J., Sey, I. C. M., Bakuli, A., Rachow, A., Geldmacher, C., & Sutherland, J. S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.740933 · Cited by 24 · see citing works
Metabolic Sex Dimorphism of the Brain at the Gene, Cell, and Tissue Level
Lee, J. W., Profant, M. R., & Wang, C. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100853 · Cited by 23 · see citing works
Myelin-reactive B cells exacerbate CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner
Fazazi, M. R., Doss, P. M. I. A., Pereira, R., Fudge, N., Regmi, A., Joly-Beauparlant, C., Akbar, I., Yeola, A. P., Mailhot, B., Baillargeon, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49259-0 · Cited by 21 · see citing works
Self-citationMcCombe, P., & Greer, J. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1059833 · Cited by 21 · see citing works
Álvarez‐Sánchez, N., & Dunn, S. E. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_324 · Cited by 19 · see citing works
Bobotis, B. C., Khakpour, M., Braniff, O., de Andrade, E. G., Gargus, M., Allen, M., Carrier, M., Baillargeon, J., Rangachari, M., & Tremblay, M.-È. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03341-6 · Cited by 17 · see citing works
Self-citationARID3a from the ARID family: structure, role in autoimmune diseases and drug discovery
Guo, C.-C., Xu, H. E., & Ma, X. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01134-2 · Cited by 17 · see citing works
KOCHKARIAN, T., Nagy, H. I., & Li, Q. (2025) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00016.2025 · Cited by 17 · see citing works
Umair, M., Fazazi, M. R., & Rangachari, M. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0202 · Cited by 14 · see citing works
Self-citationFaraji, J., Bettenson, D., Babatunde, S., Gangur-Powell, T., Yong, V. W., & Metz, G. A. S. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100477 · Cited by 12 · see citing works
Fazazi, M. R., Ruda, G. F., Brennan, P. E., & Rangachari, M. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110748 · Cited by 11 · see citing works
Self-citationAdrenoceptors as potential target for add-on immunomodulatory therapy in multiple sclerosis.
Pilipović, I., Stojić-Vukanić, Z., & Leposavić, G. (2023) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2023.108358 · Cited by 12 · see citing works
Akbar, I., Tang, R., Baillargeon, J., Roy, A.-P., Doss, P. M. I. A., Zhu, C. Y., Kuchroo, V. K., & Rangachari, M. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2300526 · Cited by 8 · see citing works
Self-citationGuak, H., Weiland, M. J., Ark, A. V., Zhai, L., Lau, K., Corrado, M., Davidson, P. J., Asiedu, E., Mabvakure, B. M., Compton, S. E., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114506 · Cited by 8 · see citing works
Itoh, N., Itoh, Y., Stiles, L., & Voskuhl, R. R. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1268411 · Cited by 6 · see citing works
Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnic, N. I., Djordjevic, J. D., & Leposavić, G. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01246-z · Cited by 5 · see citing works
Faraji, J., Bettenson, D., Yong, V. W., & Metz, G. A. S. (2023) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2023.578240 · Cited by 5 · see citing works
Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAEPreprint
Mouat, I. C., Allanach, J. R., Fan, V., Girard, A. M., Shanina, I., Vorobeychik, G., & Horwitz, M. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.22.453263 · Cited by 5 · see citing works
Itoh, Y., Itoh, N., Wendin, S., Higgins, N., & Voskuhl, R. R. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adq3401 · Cited by 5 · see citing works
Bustillos, C. G., Peluso, E., Sophia, L., Lechner, M. G., & Su, M. A. (2026) · Immunological Reviews · doi:10.1111/imr.70096 · Cited by 6 · see citing works
Rose, D. R., Moreno, R. J., Osman, H., Rowland, M. E., Silverman, J., Ciernia, A., & Ashwood, P. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03739-w · Cited by 2 · see citing works
Akbar, I., Doss, P. M. I. A., Patel, P., Surury, B., Baillargeon, J., Fazazi, M. R., Anderson, A. C., Rojas, O. L., Lassmann, H., & Rangachari, M. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag107 · Cited by 2 · see citing works
Self-citationFaraji, J., Gustafson, C., Bettenson, D., Negoro, H., Yong, V. W., & Metz, G. A. S. (2022) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2022.577973 · Cited by 2 · see citing works
Fazazi, M. R., Doss, P. M. I. A., Pereira, R., Fudge, N. J., Regmi, A., Joly-Beauparlant, C., Akbar, I., Yeola, A. P., Mailhot, B., Baillargeon, J., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/721696 · Cited by 1 · see citing works
Self-citationZeydan, B., Rangachari, M., & Kantarci, O. H. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1366126 · Cited by 1 · see citing works
Self-citationMcGuire, G. R., Klimas, A. S., Deegan, D. F., Calendo, G., Alapatt, C. F., Zaidi, M. R., Bottaro, A., & Engel, N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.16.706181 · Cited by 1 · see citing works
Guak, H., Weiland, M. J., Ark, A. V., Zhai, L., Lau, K. H., Mabvakure, B. M., Corrado, M., Davidson, P. J., Compton, S. E., DeCamp, L. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.28.542441
Serpine1 negatively regulates Th1 cell responses in experimental autoimmune encephalomyelitisPreprint
Akbar, I., Tang, R., Baillargeon, J., Roy, A.-P., Doss, P. M. I. A., Zhu, C. Y., Kuchroo, V. K., & Rangachari, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.13.548887
Self-citationPathak, R., Kumar, A., Ferrier, A., Burk, D., & Cormier, S. A. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104105
Aged oligodendrocyte progenitors retain the capacity to respond to an inflammatory insult.
Fresenko, E. E., Kaiser, K. E., Burson, B. J., Bahri, C. N., Ahmed, N. F., Bozik, J. B., Packer, D., Tabor, B. J., Beirowski, B., Wedemeyer, M. A., et al. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115874
Lei, Z., Yin, L., Zhang, B., Wang, Z., Wang, Y., & Bai, L. H. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06309-8
Gommerman, J. L., Akassoglou, K., Baranzini, S. E., Becher, B., Brilot, F., Castelo‐Branco, G., Dunn, S. E., Faiz, M., Flügel, A., Ghasemlou, N., et al. (2026) · Nature Reviews Neurology · doi:10.1038/s41582-026-01272-1
Self-citation
- Authors
- 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., Beauchemin, P., Ruda, G. F., Alpaugh, M., Anderson, A. C., Brennan, P. E., Droit, A., Lassmann, H., Moore, C. S., & Rangachari, M.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Memorial University of Newfoundland (CA)
- Université Laval (CA)
- University of Oxford (GB)
- Brigham and Women's Hospital (US)
- Medical University of Vienna (AT)
- Corresponding author
- Rangachari, Manu
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 34
- Issue
- 10
- Pages
- 108833
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3135046858
- Cited by
- 39
- References
- 98
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 3 · 2023: 10 · 2022: 11 · 2021: 3 · 2019: 1
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research
- Multiple Sclerosis Society of Canada
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › 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
- sex differences, multiple sclerosis, Th17 cells, experimental autoimmune encephalitis, JARID1C, interferon-gamma, CD4+ T cells, central nervous system autoimmunity, disease severity
- MeSH terms
- Animals, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Interferon-gamma, Male, Mice, Transgenic, Middle Aged, Multiple Sclerosis, Severity of Illness Index, Sex Chromosomes, CD4-Positive T-Lymphocytes, Down-Regulation, Autoimmunity, Mice, Inbred NOD, Mice, Histone Demethylases, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells
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.
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