PMA1-containing Extracellular Vesicles of Triggers Immune Responses and Colitis Progression

Overview

Journal Gut Microbes

Date 2025 Jan 31

PMID 39886799

Authors

Zhen Xu

Shuping Qiao

Zelin Wang

Chen Peng

Yayi Hou

Baorui Liu

Guochun Cao

Tingting Wang

Affiliations

Soon will be listed here.

Abstract

() exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in from patients with IBD compared to that in healthy controls. A Crispr-Cas9-based fungal strain editing system was then used to knock out PMA1 expression in . Compared to , could not aggravate colitis. Proteomic analysis showed that PMA1 was transported by extracellular vesicles (EVs) of . PMA1-containing EVs aggravated colitis, modulated the migration of cDC2 from the lamina propria to mesenteric lymph nodes, and induced TH17 cell differentiation. Moreover, the adaptor protein CARD9 was critical in PMA1-containing EV-induced colitis, and CARD9-deficient DCs did not induce TH17 cell differentiation or IL-17A production. Mechanically, CARD9 combines with the glycolytic protein GAPDH (aa2-146 domain) through its CARD region. CARD9 deficiency led to decreased enzyme activity of GAPDH and decreased glycolysis of DCs. These findings indicate that PMA1 is a potential virulence factor responsible for the pathogenesis of colitis.

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