Transcriptomics

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Autocrine vitamin D signaling switches off pro-inflammatory programs of Th1 cells


ABSTRACT: The molecular mechanisms governing orderly shutdown and retraction of CD4+ T helper (Th)1 responses remain poorly understood. Here, we show that complement triggers contraction of Th1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor (VDR) and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated transition from pro-inflammatory IFN-γ+ Th1 cells to suppressive IL-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VDR shaped the transcriptional response to VitD. Accordingly, VitD did not induce IL-10 in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of COVID-19 patients were Th1-skewed and showed de-repression of genes down-regulated by VitD, either from lack of substrate (VitD deficiency) and/or abnormal regulation of this system.

ORGANISM(S): Homo sapiens

PROVIDER: GSE154741 | GEO | 2021/10/19

REPOSITORIES: GEO

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