Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Scientis Pharma Inc., NY, NY, USA.
Commun Biol. 2022 Feb 24;5(1):162. doi: 10.1038/s42003-022-03109-1.
T helper 17 (Th17) cells develop in response to T cell receptor signals (TCR) in the presence of specific environments, and produce the inflammatory cytokine IL17A. These cells have been implicated in a number of inflammatory diseases and represent a potential target for ameliorating such diseases. The kinase ITK, a critical regulator of TCR signals, has been shown to be required for the development of Th17 cells. However, we show here that lung inflammation induced by Saccharopolyspora rectivirgula (SR) induced Hypersensitivity pneumonitis (SR-HP) results in a neutrophil independent, and ITK independent Th17 responses, although ITK signals are required for γδ T cell production of IL17A. Transcriptomic analysis of resultant ITK independent Th17 cells suggest that the SR-HP-induced extrinsic inflammatory signals may override intrinsic T cell signals downstream of ITK to rescue Th17 responses in the absence of ITK. These findings suggest that the ability to pharmaceutically target ITK to suppress Th17 responses may be dependent on the type of inflammation.
辅助性 T 细胞 17（Th17）细胞在特定环境下，响应 T 细胞受体信号（TCR）而发育，并产生炎症细胞因子 IL17A。这些细胞与许多炎症性疾病有关，代表了改善此类疾病的潜在目标。激酶 ITK 是 TCR 信号的关键调节因子，已被证明是 Th17 细胞发育所必需的。然而，我们在这里表明，由嗜热放线菌（SR）引起的肺炎症导致的过敏性肺炎（SR-HP）导致中性粒细胞非依赖性和 ITK 非依赖性 Th17 反应，尽管 ITK 信号对于 γδ T 细胞产生 IL17A 是必需的。对产生的 ITK 非依赖性 Th17 细胞的转录组分析表明，SR-HP 诱导的外在炎症信号可能会覆盖 ITK 下游的内在 T 细胞信号，从而在没有 ITK 的情况下挽救 Th17 反应。这些发现表明，用药物靶向 ITK 抑制 Th17 反应的能力可能取决于炎症的类型。
