title: IL-21 and IL-21 receptor expression in lymphocytes and neurons in multiple sclerosis brain.
abstract: IL-17-producing CD4(+) T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS). In addition to IL-17, Th-17 cells can also express IL-21, IL-22, and IL-6 under Th-17-polarizing conditions (IL-6 and transforming growth factor-β). In this study we investigated IL-21 and IL-21 receptor (IL-21R) expression in MS lesions by in situ hybridization and immunohistochemistry. We detected strongly IL-21(+) infiltrating cells predominantly in acute but also in chronic active white matter MS lesions in which IL-21 expression was restricted to CD4(+) cells. In contrast, IL-21R was much more broadly distributed on CD4(+), CD19(+), and CD8(+) lymphocytes but not major histocompatibility complex class-II(+) macrophages/microglia. Interestingly, in cortical areas we detected both IL-21 and IL-21R expression by neurons. These findings suggest role(s) for IL-21 in both the acute and chronic stages of MS via direct effects on T and B lymphocytes and, demonstrated for the first time, also on neurons.
authors.affiliation: Department of Neuropathology, Weatherall Institute of Molecular Medicine, Oxford Radcliffe NHS Trust, Oxford, United Kingdom.
authors.forename: John S
authors.initials: JS
authors.lastname: Tzartos
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Craner
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Friese
authors.forename: Karen B
authors.initials: KB
authors.lastname: Jakobsen
authors.forename: Jia
authors.initials: J
authors.lastname: Newcombe
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.forename: Lars
authors.initials: L
authors.lastname: Fugger
mesh_terms: D000208:Acute Disease; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002908:Chronic Disease; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D018941:Antigens, CD19; C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D012333:RNA, Messenger; D000098546:Interleukin-21