A. faecalis induces intestinal T helper 17 cells by promoting E3 ubiquitin ligase Trim21-mediated E3 ubiquitin ligase Fbxw7 degradation

Segmented filamentous bacteria are essential for intestinal T helper 17 (Th17) cell induction, but their colonization in the adult intestine is controversial. Therefore, whether there are gut microbiota (GMs) that mediate Th17 cell generation in humans of different ages is elusive. Here, we reported that colonization of ubiquitous Alcaligenes faecalis was sufficient to induce intestinal Th17 cells. Alcaligenes faecalis proteins were endocytosed by CD4⁺ T cells in a manner dependent on the small GTPase CDC42, inhibiting the interaction between E2 ubiquitin-conjugating enzyme Ube2w and E3 ubiquitin ligase Trim21, thereby reducing Trim21 self-ubiquitination and degradation, which increased Trim21-induced E3 ubiquitin ligase Fbxw7 degradation and JunB accumulation, subsequently promoting Ahr and Rorc transcription, thus enhancing intestinal Th17 cell differentiation. Furthermore, outer membrane vesicles from Alcaligenes faecalis also induced intestinal Th17 cells in a Trim21-Fbxw7-axis-dependent manner. Altogether, these results reveal a vital role for the Trim21-Fbxw7 axis in intestinal Th17 cell enrichments among most humans.