Integration of Th17- and lymphotoxin-derived signals initiates meningeal-resident stromal cell remodeling to propagate neuroinflammation.
Open accessAbstract
Tertiary lymphoid tissues (TLTs) have been observed in the meninges of multiple sclerosis (MS) patients, but the stromal cells and molecular signals that support TLTs remain unclear. Here, we show that T helper 17 (Th17) cells induced robust TLTs within the brain meninges that were associated with local demyelination during experimental autoimmune encephalitis (EAE). Th17-cell-induced TLTs were underpinned by a network of stromal cells producing extracellular matrix proteins and chemokines, enabling leukocytes to reside within, rather than simply transit through, the meninges. Within the CNS, interactions between lymphotoxin αβ (LTαβ) on Th17 cells and LTβR on meningeal radio-resistant cells were necessary for the propagation of de novo interleukin-17 responses, and activated T cells from MS patients expressed elevated levels of LTβR ligands. Therefore, input from both Th17 cells and the lymphotoxin pathway induce the formation of an immune-competent stromal cell niche in the meninges.
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The presentation of MS induced leptomeningeal inflammation can be variable, ranging from disorganized collections of immune cells to organized ectopic lymphoid follicle-like structures, and these ectopic lymph structures are potentiated by leptomeningeal fibroblasts which form a reticular cell network consisting of activated fibroblasts in a scaffold-like structure that might be driven by a subset
“The presentation of MS induced leptomeningeal inflammation can be variable, ranging from disorganized collections of immune cells to organized ectopic lymphoid follicle-like structures”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Pikor et al., 2015
Cites
Structural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413 · see citing works
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 · cited 2× · see citing works
“…cytokines both in vitro and in vivo and that the LT pathway was required for optimal induced expression of Tgfb, a vital factor for Th17 cell differentiation (Veldhoen et al., 2006), we hypothesized that LTbR-dependent signals might influence meningeal CD4+ T cell responses in the CNS.”
BackgroundPericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises
Armulik, A., Genové, G., & Betsholtz, C. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.07.001 · Cited by 2,653 · see citing works
Magliozzi, R., Howell, O. W., Vora, A., Serafini, B., Nicholas, R. S., Puopolo, M., Reynolds, R., & Aloisi, F. (2006) · Brain · doi:10.1093/brain/awm038 · Cited by 1,444 · see citing works
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
International Multiple Sclerosis Genetics Consortium (IMSGC) (2013) · Nature Genetics · doi:10.1038/ng.2770 · Cited by 1,386 · see citing works
Inflammatory cortical demyelination in early multiple sclerosis.
Lucchinetti, C. F., Popescu, B. F. G., Bunyan, R. F., Moll, N. M., Roemer, S. F., Lassmann, H., Brück, W., Parisi, J. E., Scheithauer, B. W., Giannini, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1100648 · Cited by 1,103 · see citing works
Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression
Matsushita, T., Yanaba, K., Bouaziz, J., Fujimoto, M., & Tedder, T. F. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36030 · Cited by 914 · see citing works
Lymphoid neogenesis in chronic inflammatory diseases
Aloisi, F., & Pujol‐Borrell, R. (2006) · Nature reviews. Immunology · doi:10.1038/nri1786 · Cited by 909 · see citing works
Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions.
Bartholomäus, I., Kawakami, N., Odoardi, F., Schläger, C., Miljkovic, D., Ellwart, J. W., Klinkert, W. E. F., Flügel-Koch, C., Issekutz, T. B., Wekerle, H., et al. (2009) · Nature · doi:10.1038/nature08478 · Cited by 685 · see citing works
Th17 Cells Induce Ectopic Lymphoid Follicles in Central Nervous System Tissue Inflammation
Peters, A., Pitcher, L. A., Sullivan, J. M., Mitsdoerffer, M., Acton, S. E., Franz, B., Wucherpfennig, K., Turley, S., Carroll, M. C., Sobel, R. A., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.10.015 · Cited by 480 · see citing works
Malhotra, D., Fletcher, A. L., Astarita, J. L., Lukacs‐Kornek, V., Tayalia, P., González, S., Elpek, K. G., Chang, S. K., Knoblich, K., Hemler, M. E., et al. (2012) · Nature Immunology · doi:10.1038/ni.2262 · Cited by 454 · see citing works
Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors
Kräutler, N. J., Kana, V., Kranich, J., Tian, Y., Perera, D., Lemm, D., Schwarz, P., Armulik, A., Browning, J. L., Tallquist, M. D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.032 · Cited by 397 · see citing works
Intrinsic Lymphotoxin-β Receptor Requirement for Homeostasis of Lymphoid Tissue Dendritic Cells
Kabashima, K., Banks, T. A., Ansel, K. M., Lu, T. T., Ware, C. F., & Cyster, J. G. (2005) · Immunity · doi:10.1016/j.immuni.2005.02.007 · Cited by 327 · see citing works
B cell homeostasis and follicle confines are governed by fibroblastic reticular cells
Cremasco, V., Woodruff, M. C., Onder, L., Cupovic, J., Nieves-Bonilla, J. M., Schildberg, F. A., Chang, J. E., Cremasco, F., Harvey, C. J., Wucherpfennig, K. W., et al. (2014) · Nature Immunology · doi:10.1038/ni.2965 · Cited by 278 · see citing works
Drayton, D. L., Ying, X., Lee, J., Lesslauer, W., & Ruddle, N. H. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021761 · Cited by 251 · see citing works
Chai, Q., Onder, L., Scandella, E., Gil‐Cruz, C., Perez‐Shibayama, C., Cupovic, J., Danuser, R., Sparwasser, T. D., Luther, S. A., Thiel, V., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.03.012 · Cited by 250 · see citing works
Hu, D., Mohanta, S. K., Yin, C., Peng, L., Ma, Z., Srikakulapu, P., Grassia, G., MacRitchie, N. A., Dever, G., Gordon, P., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.05.015 · Cited by 224 · see citing works
Inflammation-induced formation of fat-associated lymphoid clusters
Bénézech, C., Luu, N. T., Walker, J. A., Kruglov, A., Loo, Y., Nakamura, K., Zhang, Y., Nayar, S., Jackson-Jones, L. H., Flores‐Langarica, A., et al. (2015) · Nature Immunology · doi:10.1038/ni.3215 · Cited by 219 · see citing works
Fleige, H., Ravens, S., Moschovakis, G. L., Bölter, J., Willenzon, S., Sutter, G., Häußler, S., Kalinke, U., Prinz, I., & Förster, R. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131737 · Cited by 209 · see citing works
Targeted depletion of lymphotoxin-α–expressing TH1 and TH17 cells inhibits autoimmune disease
Chiang, E. Y., Kolumam, G. A., Yu, X., Francesco, M. R., Ivelja, S., Peng, I., Gribling, P., Shu, J., Lee, W. P., Refino, C. J., et al. (2009) · Nature Medicine · doi:10.1038/nm.1984 · Cited by 182 · see citing works
Mohan, H., Krumbholz, M., Sharma, R. D., Eisele, S. C., Junker, A., Sixt, M., Newcombe, J., Wekerle, H., Hohlfeld, R., Lassmann, H., et al. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00399.x · Cited by 160 · see citing works
Fine-tuning of dendritic cell biology by the TNF superfamily
deLuca, L. S., & Gommerman, J. L. (2012) · Nature reviews. Immunology · doi:10.1038/nri3193 · Cited by 154 · see citing works
van Horssen, J., Bø, L., Vos, C. M. P., Virtanen, I., & de Vries, H. E. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000173894.09553.13 · Cited by 129 · see citing works
A role for Th17 cells in the regulation of tertiary lymphoid follicles
Grogan, J. L., & Ouyang, W. (2012) · European Journal of Immunology · doi:10.1002/eji.201242656 · Cited by 95 · see citing works
Mead, R. J., Neal, J., Griffiths, M., Linington, C., Botto, M., Lassmann, H., & Morgan, B. P. (2003) · Laboratory Investigation · doi:10.1038/labinvest.3700015 · Cited by 93 · see citing works
Lu, T. T., & Browning, J. L. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00047 · Cited by 88 · see citing works
Cabezas, S. C., Griguoli, M., Rosicarelli, B., Magliozzi, R., Ria, F., Serafini, B., & Aloisi, F. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.06.015 · Cited by 86 · see citing works
A role for surface lymphotoxin in experimental autoimmune encephalomyelitis independent of LIGHT
Gommerman, J. L., Giza, K., Perper, S. J., Sizing, I., Ngam-ek, A., Nickerson‐Nutter, C. L., & Browning, J. L. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18648 · Cited by 63 · see citing works
Neo-Lymphoid Aggregates in the Adult Liver Can Initiate Potent Cell-Mediated Immunity
Greter, M., Hofmann, J., & Becher, B. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000109 · Cited by 39 · see citing works
Küerten, S., GRUPPE, T. L., LAURENTIUS, L.-M., KIRCH, C., Tary‐Lehmann, M., Lehmann, P., & Addicks, K. (2011) · Apmis · doi:10.1111/j.1600-0463.2011.02744.x · Cited by 32 · see citing works
deLuca, L. S., Pikor, N. B., O’Leary, J., Galicia, G., Ward, L. A., Defreitas, D., Finlay, T. M., Ousman, S. S., Osborne, L. R., & Gommerman, J. L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902881 · Cited by 32 · see citing works
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Sun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,060 · see citing works
The role of peripheral immune cells in the CNS in steady state and disease
Prinz, M., & Priller, J. (2017) · Nature Neuroscience · doi:10.1038/nn.4475 · Cited by 657 · see citing works
Fibroblasts as immune regulators in infection, inflammation and cancer
Davidson, S., Coles, M. C., Thomas, T. R., Kollias, G. A., Ludewig, B., Turley, S. J., Brenner, M. B., & Buckley, C. D. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00540-z · Cited by 612 · see citing works
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Li, X., Bechara, R., Zhao, J., McGeachy, M. J., & Gaffen, S. L. (2019) · Nature Immunology · doi:10.1038/s41590-019-0514-y · Cited by 554 · see citing works
γδ T cells in tissue physiology and surveillance
Ribot, J. C., Lopes, N., & Silva-Santos, B. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00452-4 · Cited by 532 · see citing works
Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10
Rojas, O. L., Pröbstel, A.-K., Porfilio, E. A., Wang, A. A., Charabati, M., Sun, T., Lee, D. S. W., Galicia, G., Ramaglia, V., Ward, L. A., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.035 · Cited by 382 · see citing works
Alves de Lima, K., Rustenhoven, J., & Kipnis, J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102319-103410 · Cited by 348 · see citing works
Lymph node stromal cells: cartographers of the immune system
Krishnamurty, A. T., & Turley, S. J. (2020) · Nature Immunology · doi:10.1038/s41590-020-0635-3 · Cited by 338 · see citing works
Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory
Ribeiro, M., Brigas, H. C., Temido-Ferreira, M., Pousinha, P. A., Regen, T., Santa, C., Coelho, J. E., Marques-Morgado, I., Valente, C. A., Omenetti, S., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aay5199 · Cited by 335 · see citing works
The roles of tertiary lymphoid structures in chronic diseases
Sato, Y., Siliņa, K., van den Broek, M. F., Hirahara, K., & Yanagita, M. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00706-z · Cited by 326 · see citing works
Advances in Meningeal Immunity
Rua, R., & McGavern, D. B. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.04.003 · Cited by 326 · see citing works
IL-17+ γδ T cells as kick-starters of inflammation
Papotto, P. H., Ribot, J. C., & Silva‐Santos, B. (2017) · Nature Immunology · doi:10.1038/ni.3726 · Cited by 305 · see citing works
Role of B Cells in Multiple Sclerosis and Related Disorders
Comı, G., Bar‐Or, A., Lassmann, H., Uccelli, A., Hartung, H., Montalbán, X., Sørensen, P. S., Hohlfeld, R., & Hauser, S. L. (2020) · Annals of Neurology · doi:10.1002/ana.25927 · Cited by 289 · see citing works
Rodriguez, A. B., Peske, J. D., Woods, A. N., Leick, K. M., Mauldin, I. S., Meneveau, M. O., Young, S. J., Lindsay, R. S., Melssen, M. M., Cyranowski, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109422 · Cited by 277 · see citing works
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Korn, T., & Kallies, A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.144 · Cited by 268 · see citing works
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Brigas, H. C., Ribeiro, M. A., Coelho, J. E., Gomes, R., Gómez‐Murcia, V., Carvalho, K., Faivre, É., Costa-Pereira, S., Darrigues, J., de Almeida, A. A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109574 · Cited by 232 · see citing works
Immune Cell Infiltration and Tertiary Lymphoid Structures as Determinants of Antitumor Immunity
Engelhard, V. H., Rodriguez, A. B., Mauldin, I. S., Woods, A. N., Peske, J. D., & Slingluff, C. L. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701269 · Cited by 230 · see citing works
Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology
Nayar, S., Campos, J., Smith, C. G., Iannizzotto, V., Gardner, D. H., Mourcin, F., Roulois, D., Turner, J., Sylvestre, M., Asam, S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905301116 · Cited by 203 · see citing works
Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation
Barone, F., Gardner, D. H., Nayar, S., Steinthal, N., Buckley, C. D., & Luther, S. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00477 · Cited by 193 · see citing works
Emerging roles for CNS fibroblasts in health, injury and disease
Dorrier, C., Jones, H. E., Pintarić, L., Siegenthaler, J. A., & Daneman, R. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00525-w · Cited by 194 · see citing works
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Hwang, J. Y., Randall, T. D., & Silva-Sánchez, A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00258 · Cited by 190 · see citing works
Tertiary Lymphoid Structures: Autoimmunity Goes Local
Pipi, E., Nayar, S., Gardner, D. H., Colafrancesco, S., Smith, C. G., & Barone, F. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01952 · Cited by 184 · see citing works
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de Graça, C. G., van Baarsen, L. G. M., & Mebius, R. E. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2000873 · Cited by 179 · see citing works
B cells in central nervous system disease: diversity, locations and pathophysiology
Jain, R. W., & Yong, V. W. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00652-6 · Cited by 180 · see citing works
Jones, G. W., Hill, D. G., & Jones, S. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00401 · Cited by 167 · see citing works
Molecular anatomy of adult mouse leptomeninges
Pietilä, R., Del Gaudio, F., He, L., Vázquez-Liébanas, E., Vanlandewijck, M., Muhl, L., Mocci, G., Bjørnholm, K. D., Lindblad, C., Fletcher-Sandersjöö, A., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.09.002 · Cited by 145 · see citing works
Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease
Derk, J., Jones, H. E., Como, C., Pawlikowski, B., & Siegenthaler, J. A. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703944 · Cited by 120 · see citing works
“…in MS are potentiated by leptomeningeal fibroblasts which form a reticular cell network consisting of activated fibroblasts in a scaffold-like structure, and that these fibroblasts “scaffolds” might be driven by a subset of meningeal fibroblast that express podoplanin (Pikor et al., 2015, 2017).”
BackgroundIL-17 in the Pathogenesis of Disease: Good Intentions Gone Awry
Majumder, S., & McGeachy, M. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101819-092536 · Cited by 131 · see citing works
Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases
Pan, Z., Zhu, T., Liu, Y., & Zhang, N. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.850998 · Cited by 130 · see citing works
Pathogenic T cell cytokines in multiple sclerosis
Wagner, C. A., Roqué, P. J., & Goverman, J. M. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190460 · Cited by 123 · see citing works
A short field guide to fibroblast function in immunity
Buechler, M. B., & Turley, S. J. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2017.11.001 · Cited by 121 · see citing works
Liu, Y., Ye, S., He, S., Chi, D., Wang, X., Wen, Y., Ma, D., Nie, R., Xiang, P., Zhou, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52153-4 · Cited by 127 · see citing works
T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
Kwong, B., Rua, R., Gao, Y., Flickinger, J. C., Wang, Y., Kruhlak, M. J., Zhu, J., Vivier, É., McGavern, D. B., & Lazarevic, V. (2017) · Nature Immunology · doi:10.1038/ni.3816 · Cited by 114 · see citing works
Fibroblastic reticular cells at the nexus of innate and adaptive immune responses
Perez‐Shibayama, C., Gil‐Cruz, C., & Ludewig, B. (2019) · Immunological Reviews · doi:10.1111/imr.12748 · Cited by 111 · see citing works
Pikor, N. B., Prat, A., Bar‐Or, A., & Gommerman, J. L. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00657 · Cited by 108 · see citing works
Tertiary Lymphoid Organs in Central Nervous System Autoimmunity
Mitsdoerffer, M., & Peters, A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00451 · Cited by 108 · see citing works
Bălașa, R., Bărcuţean, L., Bălașa, A. F., Moțățăianu, A., Roman-Filip, C., & Manu, D. R. (2020) · Human Immunology · doi:10.1016/j.humimm.2020.02.009 · Cited by 111 · see citing works
IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
Lu, B., Liu, M., Wang, J., Fan, H., Yang, D., Zhang, L., Gu, X., Nie, J., Chen, Z., Corbett, A. J., et al. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0273-y · Cited by 106 · see citing works
IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival
Majumder, S., Amatya, N., Revu, S. K., Jawale, C. V., Wu, D., Rittenhouse, N., Menk, A. V., Kupul, S., Du, F., Raphael, I., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0367-4 · Cited by 103 · see citing works
CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer
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Kaufmann, M., Evans, H. G., Schaupp, A.-L., Engler, J. B., Kaur, G., Willing, A., Kursawe, N., Schubert, C., Attfield, K. E., Fugger, L. H., et al. (2021) · Med · doi:10.1016/j.medj.2021.01.006 · Cited by 95 · see citing works
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Ghonim, M. A., Boyd, D. F., Flerlage, T., & Thomas, P. G. (2023) · Journal of Clinical Investigation · doi:10.1172/jci170499 · Cited by 87 · see citing works
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Bhargava, P., Kim, S., Reyes, A. A., Grenningloh, R., Boschert, U., Absinta, M., Pardo, C. A., van Zijl, P. C. M., Zhang, J., & Calabresi, P. A. (2021) · Brain · doi:10.1093/brain/awab045 · Cited by 81 · see citing works
Jamaly, S., Rakaee, M., Abdi, R., Tsokos, G. C., & Fenton, K. A. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102980 · Cited by 79 · see citing works
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Bery, A. I., Shepherd, H. M., Li, W., Krupnick, A. S., Gelman, A. E., & Kreisel, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04388-x · Cited by 74 · see citing works
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Yang, J.-X., Wang, H., Chen, J.-Z., Li, H., Hu, J.-C., Yu, A.-A., Wen, J., Chen, S., Lai, W.-D., Wang, S., et al. (2022) · Frontiers in Pain Research · doi:10.3389/fpain.2022.946846 · Cited by 74 · see citing works
Kobayashi, Y., & Watanabe, T. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00316 · Cited by 72 · see citing works
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Ghosh, D., & Stumhofer, J. S. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.4ri1020-713r · Cited by 71 · see citing works
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Luo, S., Zhu, R., Yu, T., Fan, H., Hu, Y., Mohanta, S. K., & Hu, D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02938 · Cited by 70 · see citing works
Lymphoid Aggregates in the CNS of Progressive Multiple Sclerosis Patients Lack Regulatory T Cells
Bell, L., Lenhart, A., Rosenwald, A., Monoranu, C. M., & Berberich‐Siebelt, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03090 · Cited by 67 · see citing works
The Ins and Outs of Central Nervous System Inflammation—Lessons Learned from Multiple Sclerosis
Ramaglia, V., Rojas, O. L., Naouar, I., & Gommerman, J. L. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-124155 · Cited by 69 · see citing works
Alsughayyir, J., Pettigrew, G. J., & Motallebzadeh, R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01639 · Cited by 60 · see citing works
Song, J., Wang, H., Zhang, Y., Cao, P.-P., Liao, B., Wang, Z.-Z., Shi, L.-L., Yao, Y., Zhai, G.-T., Wang, Z.-C., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.10.014 · Cited by 60 · see citing works
Adventitial Cuffs: Regional Hubs for Tissue Immunity
Dahlgren, M. W., & Molofsky, A. B. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.08.002 · Cited by 58 · see citing works
Balzano, T., Forteza, J., Molina, P., Giner, J., Monzó, A., Sancho-Jiménez, J., Urios, A., Montoliu, C., & Felipo, V. (2018) · Scientific Reports · doi:10.1038/s41598-018-21399-6 · Cited by 57 · see citing works
Luo, R., Cheng, Y., Chang, D., Liu, T., Liu, L., Pei, G., Zhang, N., Wang, Z., Guo, K., Chen, W., et al. (2020) · Theranostics · doi:10.7150/thno.48624 · Cited by 55 · see citing works
Ahmed, S. M., Fransen, N. L., Touil, H., Michailidou, I., Huitinga, I., Gommerman, J. L., Bar‐Or, A., & Ramaglia, V. (2022) · JCI Insight · doi:10.1172/jci.insight.151683 · Cited by 52 · see citing works
Dynamic fibroblast–immune interactions shape recovery after brain injury
Ewing-Crystal, N. A., Mroz, N. M., Larpthaveesarp, A., Lizama, C. O., Pennington, R., Chiaranunt, P., Dennis, J. I., Chang, A. A., Merrill, E. D., Caryotakis, S. E., et al. (2025) · Nature · doi:10.1038/s41586-025-09449-2 · Cited by 56 · see citing works
The pathogenesis of bornaviral diseases in mammals
Tizard, I. R., Ball, J. M., Stoica, G., & Payne, S. (2016) · Animal Health Research Reviews · doi:10.1017/s1466252316000062 · Cited by 53 · see citing works
Stromal cells in tertiary lymphoid structures: Architects of autoimmunity
Asam, S., Nayar, S., Gardner, D. H., & Barone, F. (2021) · Immunological Reviews · doi:10.1111/imr.12987 · Cited by 52 · see citing works
The role of the complement system in Multiple Sclerosis: A review
Saez-Calveras, N., & Stüve, O. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.970486 · Cited by 49 · see citing works
Morgan, B. P., Gommerman, J. L., & Ramaglia, V. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.600656 · Cited by 47 · see citing works
Dendritic cells in central nervous system autoimmunity
Sie, C., & Korn, T. (2016) · Seminars in Immunopathology · doi:10.1007/s00281-016-0608-7 · Cited by 47 · see citing works
Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?
Negron, A., Stüve, O., & Forsthuber, T. G. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.607766 · Cited by 47 · see citing works
Mitsdoerffer, M., Liberto, G. D., Dötsch, S., Sie, C., Wagner, I., Pfaller, M., Kreutzfeldt, M., Fräßle, S. P., Aly, L., Knier, B., et al. (2021) · Brain · doi:10.1093/brain/awab093 · Cited by 46 · see citing works
Serafini, B., Rosicarelli, B., Veroni, C., Zhou, L., Reali, C., & Aloisi, F. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw063 · Cited by 46 · see citing works
New advances in CNS immunity against viral infection
Manglani, M., & McGavern, D. B. (2017) · Current Opinion in Virology · doi:10.1016/j.coviro.2017.12.003 · Cited by 45 · see citing works
Targeting senescence to delay progression of multiple sclerosis
Oost, W., Talma, N., Meilof, J. F., & Laman, J. D. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1686-x · Cited by 45 · see citing works
Lymphotoxin-alpha expression in the meninges causes lymphoid tissue formation and neurodegeneration
Bates, R. E. J., Browne, E., Schalks, R., Jacobs, H., Tan, L. Y., Parekh, P., Magliozzi, R., Calabrese, M., Mazarakis, N. D., & Reynolds, R. (2022) · Brain · doi:10.1093/brain/awac232 · Cited by 42 · see citing works
Harp, C. R. P., Archambault, A. S., Cheung, M. D., Williams, J. W., Czepielewski, R. S., Duncker, P. C., Kilgore, A. J., Miller, A. T., Segal, B. M., Kim, A. H. J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909098116 · Cited by 42 · see citing works
Lymphotoxin in physiology of lymphoid tissues - implication for antiviral defense
Koroleva, E., Fu, Y.-X., & Tumanov, A. (2016) · Cytokine · doi:10.1016/j.cyto.2016.08.018 · Cited by 34 · see citing works
Tertiary lymphoid organs in systemic autoimmune diseases: pathogenic or protective?
Shipman, W. D., Dasoveanu, D., & Lu, T. T. (2017) · F1000Research · doi:10.12688/f1000research.10595.1 · Cited by 40 · see citing works
Leptomeningeal inflammation in multiple sclerosis: Insights from animal and human studies
Wicken, C., Nguyen, J. V., Karna, R., & Bhargava, P. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.09.025 · Cited by 39 · see citing works
Ma, T., Wang, F., Xu, S., & Huang, J. H. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.01.028 · Cited by 37 · see citing works
Wilharm, A., Brigas, H. C., Sandrock, I., Ribeiro, M. A., Amado, T., Reinhardt, A., Demera, A., Hoenicke, L., Strowig, T., Carvalho, T., et al. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0330-6 · Cited by 40 · see citing works
Tertiary Lymphoid Structures in the Central Nervous System: Implications for Glioblastoma
van de Walle, T., Vaccaro, A., Ramachandran, M., Pietilä, I., Essand, M., & Dimberg, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.724739 · Cited by 37 · see citing works
Contribution of B cells to cortical damage in multiple sclerosis
Bhargava, P., Hartung, H.-P., & Calabresi, P. A. (2022) · Brain · doi:10.1093/brain/awac233 · Cited by 36 · see citing works
Nayar, S., Pontarini, E., Campos, J., Berardicurti, O., Smith, C. G., Asam, S., Gardner, D. H., Colafrancesco, S., Lucchesi, D., Coleby, R., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03344-6 · Cited by 35 · see citing works
Wang, A. A., Luessi, F., Neziraj, T., Pössnecker, E., Zuo, M., Engel, S., Hanuscheck, N., Florescu, A., Bugbee, E., Xianjie, I., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0295 · Cited by 35 · see citing works
Shen, S., Cui, Y., Li, M., Yu, K., Zhu, Q., Zhang, X., Shen, W., Li, H., Jiang, H., Li, M., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae167 · Cited by 35 · see citing works
Perivascular stromal cells: Directors of tissue immune niches
Sbierski‐Kind, J., Mroz, N. M., & Molofsky, A. B. (2021) · Immunological Reviews · doi:10.1111/imr.12984 · Cited by 33 · see citing works
Regulation of Lymph Node Vascular–Stromal Compartment by Dendritic Cells
Dasoveanu, D., Shipman, W. D., Chia, D. J., Chyou, S., & Lu, T. T. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.013 · Cited by 34 · see citing works
Central Nervous System Fibroblast-Like Cells in Stroke and Other Neurological Disorders
Xu, L., & Yao, Y. (2021) · Stroke · doi:10.1161/strokeaha.120.033431 · Cited by 34 · see citing works
Shou, Y., Koroleva, E. P., Spencer, C. M., Shein, S. A., Korchagina, A. A., Yusoof, K. A., Parthasarathy, R., Leadbetter, E. A., Akopian, A. N., Muñoz, A. R., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.712632 · Cited by 34 · see citing works
Stromal cell niches in the inflamed central nervous system.
Pikor, N. B., Cupovic, J., Onder, L., Gommerman, J. L., & Ludewig, B. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601566 · Cited by 33 · see citing works
Self-citationSiponimod therapy implicates Th17 cells in a preclinical model of subpial cortical injury
Ward, L. A., Lee, D. S. W., Sharma, A. K., Wang, A. A., Naouar, I., Xianjie, I., Pikor, N. B., Nuesslein‐Hildesheim, B., Ramaglia, V., & Gommerman, J. L. (2019) · JCI Insight · doi:10.1172/jci.insight.132522 · Cited by 32 · see citing works
Li, C., Lam, E., Perez‐Shibayama, C., Ward, L. A., Zhang, J., Lee, D. S. W., Nguyen, A., Ahmed, M., Brownlie, E., Korneev, K. V., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aax1027 · Cited by 32 · see citing works
Bcl6 controls meningeal Th17–B cell interaction in murine neuroinflammation
Hartlehnert, M., Börsch, A., Li, X., Burmeister, M., Gerwien, H., Schafflick, D., Heming, M., Lu, I., Narayanan, V., Strecker, J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023174118 · Cited by 31 · see citing works
Age-dependent gray matter demyelination is associated with leptomeningeal neutrophil accumulation
Zuo, M., Fettig, N. M., Bernier, L., Pössnecker, E., Spring, S., Pu, A., Xianjie, I., Lee, D. S., Ward, L. A., Sharma, A. K., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.158144 · Cited by 31 · see citing works
Maheshwari, S., Dwyer, L., & Sîrbulescu, R. F. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106077 · Cited by 31 · see citing works
Jing, F., & Choi, E. Y. (2016) · Immune Network · doi:10.4110/in.2016.16.5.271 · Cited by 31 · see citing works
Reste, M., Ajazi, K., Sayi‐Yazgan, A., Janković, R., Bufan, B., Brandau, S., Bækkevold, E. S., Petitprez, F., Lindstedt, M., Adema, G. J., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1439413 · Cited by 30 · see citing works
Chamoun, M. N., Blumenthal, A., Sullivan, M. J., Schembri, M. A., & Ulett, G. C. (2018) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2018.1426556 · Cited by 30 · see citing works
Kee, R., Naughton, M., McDonnell, G. V., Howell, O. W., & Fitzgerald, D. C. (2022) · Biomedicines · doi:10.3390/biomedicines10102604 · Cited by 30 · see citing works
- Authors
- Pikor, N. B., Astarita, J. L., Summers-Deluca, L., Galicia, G., Qu, J., Ward, L. A., Armstrong, S., Dominguez, C. X., Malhotra, D., Heiden, B., Kay, R., Castanov, V., Touil, H., Boon, L., O’Connor, P., Bar-Or, A., Prat, A., Ramaglia, V., Ludwin, S., Turley, S. J., & Gommerman, J. L.
- Affiliations
- University of Toronto (CA)
- Harvard University (US)
- Genentech (US)
- Montreal Neurological Institute and Hospital (CA)
- University Medical Center Utrecht (NL)
- Centre Hospitalier de l’Université de Montréal (CA)
- Amsterdam UMC Location University of Amsterdam (NL)
- Queen's University (CA)
- Corresponding author
- Gommerman, Jennifer L.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 43
- Issue
- 6
- Pages
- 1160-1173
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2212030004
- Cited by
- 229
- References
- 31
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 27 · 2023: 16 · 2022: 23 · 2021: 34 · 2020: 17 · 2019: 22 · 2018: 18 · 2017: 14 · 2016: 14 · 2015: 1
- FWCI
- 12.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society of Canada
- Multiple Sclerosis Society
- U.S. Public Health Service (P01 AIO45757)
- Canadian Institutes of Health Research (MOG 67157)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074500)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tertiary lymphoid tissue, meninges, Th17 cells, lymphotoxin beta receptor, stromal cells, neuroinflammation, multiple sclerosis, experimental autoimmune encephalitis, demyelination, extracellular matrix, chemokines, leukocyte homing, IL-17
- MeSH terms
- Adult, Animals, Encephalomyelitis, Autoimmune, Experimental, Female, Flow Cytometry, Humans, Immunohistochemistry, Inflammation, Lymphotoxin-alpha, Male, Meninges, Signal Transduction, CD4-Positive T-Lymphocytes, Polymerase Chain Reaction, Stromal Cells, Mice, Knockout, Multiple Sclerosis, Relapsing-Remitting, Mice, Th17 Cells
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