Abstract:
:Microbial metabolites are an emerging class of mediators influencing CD4+ T-cell function. To advance the understanding of direct causal microbial factors contributing to Crohn's disease, we screened 139 predicted Crohn's disease-associated microbial metabolites for their bioactivity on human CD4+ T-cell functions induced by disease-associated T helper 17 (Th17) polarizing conditions. We observed 15 metabolites with CD4+ T-cell bioactivity, 3 previously reported, and 12 unprecedented. A deeper investigation of the microbe-derived metabolite, ascorbate, revealed its selective inhibition on activated human CD4+ effector T cells, including IL-17A-, IL-4-, and IFNγ-producing cells. Mechanistic assessment suggested the apoptosis of activated human CD4+ T cells associated with selective inhibition of energy metabolism. These findings suggest a substantial rate of relevant T-cell bioactivity among Crohn's disease-associated microbial metabolites, and evidence for novel modes of bioactivity, including targeting of T-cell energy metabolism.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Chang YL,Rossetti M,Vlamakis H,Casero D,Sunga G,Harre N,Miller S,Humphries R,Stappenbeck T,Simpson KW,Sartor RB,Wu G,Lewis J,Bushman F,McGovern DPB,Salzman N,Borneman J,Xavier R,Huttenhower C,Braun Jdoi
10.1038/s41385-018-0022-7subject
Has Abstractpub_date
2019-03-01 00:00:00pages
457-467issue
2eissn
1933-0219issn
1935-3456pii
10.1038/s41385-018-0022-7journal_volume
12pub_type
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