GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization
GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization
复制标题
DOI：
10.1084/jem.20091844
复制
发表时间：
2010-05-10
影响因子：
15.3
通讯作者：
Segal, Benjamin M.
中科院分区：
文献类型：
--
作者：
King, Irah L.;Kroenke, Mark A.;Segal, Benjamin M.
树突状细胞（dc）在CD4(+) T辅助细胞（Th）分化和保护性和致病性免疫的启动中发挥重要作用。粒细胞/巨噬细胞集落刺激因子（GM-CSF）是一种DC生长因子，对诱导实验性自身免疫性脑脊髓炎（EAE）等自身免疫性疾病至关重要，但其体内作用机制尚不完全明确。我们发现，在稳态和炎症条件下，GM-CSF是皮肤和周围淋巴结中放射敏感性真皮源性langerin(+)CD103(+) dc积累的直接需要。Langerin(+)CD103(+) DCs刺激幼稚髓磷脂反应性T细胞增殖并产生ifn - γ和IL-17。它们在诱导T-bet表达和促进Th1细胞分化方面优于其他DC亚群。在体内消融这一亚群赋予了对EAE的耐药性。目前的报告揭示了先前未被确定的GM-CSF在DC个体发生中的作用，并确定langerin(+)CD103(+) DC是CD4(+) T细胞介导的自身免疫性疾病的重要亚群。
Dendritic cells (DCs) play an important role in CD4(+) T helper (Th) cell differentiation and in the initiation of both protective and pathogenic immunity. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a DC growth factor critical for the induction of experimental autoimmune encephalomyelitis (EAE) and other autoimmune diseases, yet its mechanism of action in vivo is not fully defined. We show that GM-CSF is directly required for the accumulation of radiosensitive dermal-derived langerin(+)CD103(+) DCs in the skin and peripheral lymph nodes under steady-state and inflammatory conditions. Langerin(+)CD103(+) DCs stimulated naive myelin-reactive T cells to proliferate and produce IFN-gamma and IL-17. They were superior to other DC subsets in inducing expression of T-bet and promoting Th1 cell differentiation. Ablation of this subset in vivo conferred resistance to EAE. The current report reveals a previously unidentified role for GM-CSF in DC ontogeny and identifies langerin(+)CD103(+) DCs as an important subset in CD4(+) T cell-mediated autoimmune disease.