文章基本信息

标题：Microbiota-mediated skewing of tryptophan catabolism modulates CD4 + T cells in lupus-prone mice
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作者：Josephine Brown ; Georges Abboud ; Longhuan Ma 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-22
DOI：10.1016/j.isci.2022.104241
语种：English
出版社：Elsevier
摘要：SummaryA skewed tryptophan metabolism has been reported in patients with lupus. Here, we investigated the mechanisms by which it occurs in lupus-susceptible mice, and how tryptophan metabolites exacerbate T cell activation. Metabolomic analyses demonstrated that tryptophan is differentially catabolized in lupus mice compared to controls and that the microbiota played a role in this skewing. There was no evidence for differential expression of tryptophan catabolic enzymes in lupus mice, further supporting a major contribution of the microbiota to skewing. However, isolated lupus T cells processed tryptophan differently, suggesting a contribution of T cell intrinsic factors. Functionally, tryptophan and its microbial product tryptamine increased T cell metabolism and mTOR activation, while kynurenine promoted interferon gamma production, all of which have been associated with lupus. These results showed that a combination of microbial and T cell intrinsic factors promotes the production of tryptophan metabolites that enhance inflammatory phenotypes in lupus T cells.Graphical abstractDisplay OmittedHighlights•Intestinal dysbiosis skews tryptophan catabolism in lupus-prone mice•Murine lupus CD4+T cells have an intrinsically different processing of tryptophan•Tryptophan and tryptamine increase mTOR activation and metabolism in CD4+T cells•Kynurenine promotes IFNγ production in CD4+T cells from lupus-prone miceBiological sciences; Human metabolism; Immunology; Cell biology