Commensal Microbiome Expands T gamma delta 17 Cells in the Lung and Promotes Particulate Matter-Induced Acute Neutrophilia

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 gamma delta T cells and intestinal microbiome in PM-induced acute neutrophilia. gamma delta T cells are a heterogeneous population composed of T gamma delta 1, T gamma delta 2, T gamma delta 17, and naive gamma delta T cells (T gamma delta N) and commensal bacteria promote local expansion of T gamma delta 17 cells, particularly in the lung and gut without affecting their V gamma repertoire. T gamma delta 17 cells are more tissue resident than T gamma delta 1 cells, while T gamma delta N cells are circulating cells. IL-1R expression in T gamma delta 17 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-1 beta-secreting neutrophils and IL-17-producing T gamma delta 17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in gamma delta T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lung via T gamma delta 17 cells.