CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE
CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE
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DOI：
10.1038/ni1430
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发表时间：
2007-02-01
影响因子：
30.5
通讯作者：
Miller, Stephen D.
中科院分区：
文献类型：
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作者：
Bailey, Samantha L.;Schreiner, Bettina;Miller, Stephen D.
复发性实验性自身免疫性脑脊髓炎（EAE）时外周来源的CD 11b（+）髓样树突状细胞（mDCs）、浆细胞样DCs、CD 8 α（+）DCs和巨噬细胞在中枢神经系统内聚集。在由氨基酸178 - 191的蛋白脂质蛋白肽诱导的急性复发性EAE期间，对由蛋白脂质蛋白肽氨基酸139 - 151组成的复发表位特异性的转基因T细胞（139 TCR细胞）与中枢神经系统中的mDC聚集，被激活并分化为产生白细胞介素17的辅助性T细胞（TH-17细胞）。CNS mDCs可提呈内源性肽，在体外和体内驱动幼稚139 TCR细胞增殖和产生白细胞介素17。mDC独特地偏向T-H-17而不是T（H）1分化，这与它们增强的转化生长因子β 1和白细胞介素6和23的表达相关。浆细胞样DC和CD 8 α（+）DC的上级能力优于巨噬细胞，但在提呈内源性肽以诱导T-H-17细胞方面远低于mDC。我们的研究结果表明，中枢神经系统mDCs在驱动复发EAE复发的关键功能。
Peripherally derived CD11b(+) myeloid dendritic cells (mDCs), plasmacytoid DCs, CD8 alpha(+) DCs and macrophages accumulate in the central nervous system during relapsing experimental autoimmune encephalomyelitis (EAE). During acute relapsing EAE induced by a proteolipid protein peptide of amino acids 178 - 191, transgenic T cells (139TCR cells) specific for the relapse epitope consisting of proteolipid protein peptide amino acids 139 - 151 clustered with mDCs in the central nervous system, were activated and differentiated into T helper cells producing interleukin 17 (T-H-17 cells). CNS mDCs presented endogenously acquired peptide, driving the proliferation of and production of interleukin 17 by naive 139TCR cells in vitro and in vivo. The mDCs uniquely biased T-H-17 and not T(H)1 differentiation, correlating with their enhanced expression of transforming growth factor-beta 1 and interleukins 6 and 23. Plasmacytoid DCs and CD8 alpha(+) DCs were superior to macrophages but were much less efficient than mDCs in presenting endogenous peptide to induce T-H-17 cells. Our findings indicate a critical function for CNS mDCs in driving relapses in relapsing EAE.