Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells.
Nat Immunol
; 23(1): 62-74, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1514418
ABSTRACT
The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-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 VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Vitamin D
/
Interferon-gamma
/
Interleukin-10
/
Th1 Cells
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
Nat Immunol
Journal subject:
Allergy and Immunology
Year:
2022
Document Type:
Article
Affiliation country:
S41590-021-01080-3
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