The induction and function of the anti-inflammatory fate of TH17 cells
The induction and function of the anti-inflammatory fate of TH17 cells
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DOI：
10.1038/s41467-020-17097-5
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发表时间：
2020-07-03
影响因子：
16.6
通讯作者：
Gagliani, Nicola
中科院分区：
文献类型：
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作者：
Xu, Hao;Agalioti, Theodora;Gagliani, Nicola
T（H）17细胞具有环境免疫适应性：它们可以获得致病和抗炎的命运。然而，目前尚不清楚抗炎命运是否仅仅是一种残留特征，或者它是否有助于保持宿主组织的完整性。在这里，我们表明T（H）17细胞获得抗炎命运的能力是维持免疫耐受所必需的，但它削弱了对S。金黄色。此外，我们发现TGF-β通过Smad 3/Smad 4信号传导足以在T（H）17细胞中表达抗炎细胞因子IL-10。因此，我们的数据表明T（H）17细胞可塑性在维持免疫稳态中的关键功能，并剖析了解释T（H）17细胞对环境变化的功能灵活性的分子机制。产生IL-17 A的CD 4（+）T辅助细胞（T（H）17细胞）可以以特定的方式承担致病或抗炎功能。在这里，作者表明，T（H）17细胞的抗炎命运通过TGF-β信号传导和IL-10的诱导有助于宿主免疫耐受，但同时也抑制了对S.金黄色。
T(H)17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of T(H)17 cells to acquire an anti-inflammatory fate is necessary to sustain immunological tolerance, yet it impairs immune protection against S. aureus. Additionally, we find that TGF-beta signalling via Smad3/Smad4 is sufficient for the expression of the anti-inflammatory cytokine, IL-10, in T(H)17 cells. Our data thus indicate a key function of T(H)17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of T(H)17 cells with regard to environmental changes. CD4(+) T helper cells producing IL-17A (T(H)17 cells) can take on pathogenic or anti-inflammatory functions in context-specific manners. Here the authors show that the anti-inflammatory fate of T(H)17 cells contributes, via TGF-beta signaling and induction of IL-10, to host immune tolerance, but also simultaneously dampens protective immunity against S. aureus.