Microbiota-mediated skewing of tryptophan catabolism modulates CD4+ T cells in lupus-prone mice

• DOI: 10.1016/j.isci.2022.104241
• Publication Date: 2022-04-12T18:28:51Z
• Authors: Josephine Brown; Georges Abboud; Longhuan Ma; Seung-Chul Choi; Nathalie Kanda; Leilani Zeumer-Sp...; Jean Lee; Weidan Peng; Joy Cagmat; Tamas Faludi; Mansour Mohamadzadeh; Timothy Garrett; Laura Mandik-Nayak; Alexander Chervonsky; Andras Perl; Laurence Morel
• Keywords: Kynurenine pathway; Catabolism; Indoleamine 2,3-dioxygenase

A skewed tryptophan metabolism has been reported in patients with lupus. Here, we investigated the mechanisms by which it occurs lupus-susceptible mice, and how metabolites exacerbate T cell activation. Metabolomic analyses demonstrated that is differentially catabolized lupus mice compared to controls microbiota played a role this skewing. There was no evidence for differential expression of catabolic enzymes further supporting major contribution However, isolated cells processed differently, suggesting intrinsic factors. Functionally, its microbial product tryptamine increased mTOR activation, while kynurenine promoted interferon gamma production, all have associated These results showed combination factors promotes production enhance inflammatory phenotypes cells.