Th17 Cells and autoimmune encephalomyelitis (EAE/MS).
Multiple sclerosis (MS) is a CD4+ T cell-mediated autoimmune disease affecting the central nervous system. It was largely accepted that Th1 cells driven by IL-12 were pathogenic T cells in human MS and experimental autoimmune encephalomyelitis, an animal model of MS. Recent data have established that IL-17-producing CD4+ T cells, driven by IL-23 and referred to as Th17 cells, play a pivotal role in the pathogenesis of EAE. A combination of TGF-beta and IL-6 induce Th17 cell lineage commitment via expression of transcription factor RORgammat. Th17 cells and induced Foxp3+ T regulatory cells are in reciprocal position in the T cell lineage commitment governed by TGF-beta and IL-6. The vitamin A metabolite retinoic acid is involved in this process via TGF-beta dependent induction of Foxp3. We have demonstrated that human Th17 cells could be identified as CCR2+ CCR5- memory CD4+ T cells. It is becoming clear that IL-23/Th17 axis also plays an important role in the pathogenesis of various human autoimmune diseases including MS. Additionally, accumulating evidences raise a possibility that CCR2 on Th17 cells may be a therapeutic target in MS.
Aranami
Toshimasa
T
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yamamura
Takashi
T
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002454:Cell Differentiation; D004679:Encephalomyelitis / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054390:Receptors, CCR2 / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D051858:Forkhead Transcription Factors; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D054390:Receptors, CCR2; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D016212:Transforming Growth Factor beta