Priming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment.

Priming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment.
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DOI:
10.1016/j.immuni.2011.10.013
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发表时间:
2011-12-23
期刊:
影响因子:
32.4
通讯作者:
Pasare C
Pasare C
中科院分区:
医学1区
文献类型:
--
作者:
Hu W;Troutman TD;Edukulla R;Pasare C

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树突状细胞(DCs)和巨噬细胞上模式识别受体的激活导致细胞因子的分泌,这些细胞因子控制CD4 + T细胞的分化。目前的理解是,白细胞介素(IL)-6与转化生长因子 -β(TGF -β)共同作用导致辅助性T细胞17(Th17)谱系细胞的产生。在此,我们发现Th17细胞极化对细胞因子的需求取决于启动部位。虽然IL - 6在皮肤和黏膜组织中Th17细胞谱系的启动中起关键作用,但在脾脏中Th17细胞的启动并不需要它。相反,IL - 1在所有组织中对Th17细胞谱系细胞的启动都起着不可替代的作用。重要的是,我们已经证明,Th17细胞分化的IL - 6非依赖和依赖途径是由存在于各种组织中的DCs引导的。这些结果揭示了全身性、黏膜和皮肤免疫系统引导Th17细胞谱系定型的根本差异。
Activation of pattern recognition receptors on dendritic cells (DCs) and macrophages leads to secretion of cytokines that control differentiation of CD4+ T cells. The current understanding is that interleukin (IL)-6 in combination with transforming growth factor-β (TGF-β) leads to generation of T helper-17 (Th17) lineage cells. Here, we have discovered that the cytokine requirements for Th17 cell polarization depend on the site of priming. While IL-6 played a critical role in Th17 cell lineage priming in the skin and mucosal tissues, it was not required for Th17 cell priming in the spleen. In contrast, IL-1 played an irreplaceable role for priming of Th17 cell lineage cells in all tissues. Importantly, we have demonstrated that IL-6 independent and dependent pathways of Th17 cell differentiation are guided by DCs residing in various tissues. These results reveal fundamental differences by which the systemic, mucosal and cutaneous immune systems guide Th17 cell lineage commitment.
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