The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells
The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells
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DOI：
10.1016/j.immuni.2019.05.004
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发表时间：
2019-07-16
期刊：
影响因子：
32.4
通讯作者：
Stockinger, Brigitta
中科院分区：
文献类型：
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作者：
Omenetti, Sara;Bussi, Claudio;Stockinger, Brigitta
辅助性T - 17 （Th17）细胞在许多炎症性疾病中具有致病性，但也以非炎症方式支持肠道屏障的完整性。病原体诱导的炎性Th17细胞和共生体诱导的组织内稳态Th17细胞的区别尚不清楚。在这里，我们比较了Th17细胞对共生细菌（SFB）的分化和对病原体（鼠柠檬酸杆菌）的分化的特征。稳态Th17细胞对炎症细胞因子的表达几乎没有可塑性，其特征是典型的静止或记忆T细胞的代谢，并且不参与炎症过程。相比之下，感染诱导的Th17细胞对促炎细胞因子表现出广泛的可塑性，广泛播散到外周，除了炎症效应细胞典型的氧化磷酸化外，还参与有氧糖酵解。这些发现将有助于确保未来针对炎症性Th17细胞的治疗不会无意中损害常驻肠道群体。
T helper 17 (Th17) cells are pathogenic inmany inflammatory diseases, but also support the integrity of the intestinal barrier in a non-inflammatory manner. It is unclear what distinguishes inflammatory Th17 cells elicited by pathogens and tissue-resident homeostatic Th17 cells elicited by commensals. Here, we compared the characteristics of Th17 cells differentiating in response to commensal bacteria (SFB) to those differentiating in response to a pathogen (Citrobacter rodentium). Homeostatic Th17 cells exhibited little plasticity towards expression of inflammatory cytokines, were characterized by a metabolism typical of quiescent or memory T cells, and did not participate in inflammatory processes. In contrast, infection-induced Th17 cells showed extensive plasticity towards pro-inflammatory cytokines, disseminated widely into the periphery, and engaged aerobic glycolysis in addition to oxidative phosphorylation typical for inflammatory effector cells. These findings will help ensure that future therapies directed against inflammatory Th17 cells do not inadvertently damage the resident gut population.