A screen of Crohn's disease-associated microbial metabolites identifies ascorbate as a novel metabolic inhibitor of activated human T cells. Mucosal Immunol 2019 Mar;12(2):457-467
Date
04/27/2018Pubmed ID
29695840Pubmed Central ID
PMC6202286DOI
10.1038/s41385-018-0022-7Scopus ID
2-s2.0-85046035681 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
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.
Author List
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 JAuthor
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisAscorbic Acid
Cell Differentiation
Cell Respiration
Cells, Cultured
Crohn Disease
Energy Metabolism
Humans
Interferon-gamma
Interleukin-17
Interleukin-4
Lymphocyte Activation
Mass Screening
Microbiota
Th17 Cells
