A microbial metabolite, Lithocholic acid, suppresses IFN-γ and AhR expression by human cord blood CD4 T cells
Vitamin D is a well-known micronutrient that modulates immune responses by epigenetic and transcriptional regulation of target genes, such as inflammatory cytokines. Our group recently demonstrated that the most active form of vitamin D, calcitriol, reduces expression of a transcription factor known as the aryl hydrocarbon receptor (AhR) and inhibits differentiation of a pro-inflammatory T cell subset, Th9. Lithocholic acid (LCA), a secondary bile acid produced by commensal bacteria, is known to bind to and activate the vitamin D receptor (VDR) in a manner comparable to calcitriol. In this study, Naive CD4 T cells were isolated from healthy human umbilical mononuclear cells and were stimulated in the presence or absence of LCA. We determined the effect of LCA on human cord blood T cell activation by measuring IFN-{gamma} production and protein expression of IFN-{gamma} receptor-mediated signaling molecules. We found that LCA reduces production of IFN-{gamma} and decreases phosphorylation of STAT1 as well as expression of AhR, STAT1, and IRF1 by activated human cord blood CD4 T cells. LCA inhibits expression of IFN-{gamma} and reduces its receptor signaling molecules.\n\nHighlightsO_LILithocholic acid suppresses IFN{gamma} production by CD4 T cells.\nC_LIO_LILithocholic acid suppresses STAT1 and IRF1 expression by activated CD4 T cells.\nC_LIO_LILithocholic acid suppresses AhR in a comparable manner to calcitriol.\nC_LI