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共生微生物组在肺部扩增 Tγδ17 细胞,并促进颗粒物诱导的急性中性粒细胞增多。

Commensal Microbiome Expands Tγδ17 Cells in the Lung and Promotes Particulate Matter-Induced Acute Neutrophilia.

机构信息

Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.

ImmunoBiome Inc., Pohang-si, South Korea.

出版信息

Front Immunol. 2021 Mar 29;12:645741. doi: 10.3389/fimmu.2021.645741. eCollection 2021.

Abstract

Particulate matter (PM) induces neutrophilic inflammation and deteriorates the prognosis of diseases such as cardiovascular diseases, cancers, and infections, including COVID-19. Here, we addressed the role of γδ T cells and intestinal microbiome in PM-induced acute neutrophilia. γδ T cells are a heterogeneous population composed of Tγδ1, Tγδ2, Tγδ17, and naïve γδ T cells (TγδN) and commensal bacteria promote local expansion of Tγδ17 cells, particularly in the lung and gut without affecting their Vγ repertoire. Tγδ17 cells are more tissue resident than Tγδ1 cells, while TγδN cells are circulating cells. IL-1R expression in Tγδ17 cells is highest in the lung and they outnumber all the other type 17 cells such as Th17, ILC3, NKT17, and MAIT17 cells. Upon PM exposure, IL-1β-secreting neutrophils and IL-17-producing Tγδ17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in γδ T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lung Tγδ17 cells.

摘要

颗粒物(PM)可诱导中性粒细胞炎症,并使心血管疾病、癌症和感染(包括 COVID-19)等疾病的预后恶化。在这里,我们研究了 γδ T 细胞和肠道微生物群在 PM 诱导的急性中性粒细胞增多中的作用。γδ T 细胞是一个异质性群体,由 Tγδ1、Tγδ2、Tγδ17 和幼稚 γδ T 细胞(TγδN)组成,共生菌促进 Tγδ17 细胞在肺部和肠道中的局部扩增,而不影响其 Vγ 受体库。Tγδ17 细胞比 Tγδ1 细胞更具组织驻留性,而 TγδN 细胞是循环细胞。在肺部,Tγδ17 细胞中 IL-1R 的表达最高,其数量超过所有其他 17 型细胞,如 Th17、ILC3、NKT17 和 MAIT17 细胞。在 PM 暴露后,IL-1β 分泌的中性粒细胞和产生 IL-17 的 Tγδ17 细胞在气道周围相互吸引。因此,在 γδ T 细胞缺陷或无菌小鼠中,PM 诱导的中性粒细胞增多明显缓解。综上所述,这些发现表明共生微生物群促进了 PM 在肺部诱导的中性粒细胞增多,其中涉及 Tγδ17 细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb7c/8039457/09715dd284e8/fimmu-12-645741-g001.jpg

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