Nature Immunology: Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells

[sharon sanders]

• Published: 11 November 2021

Autocrine vitamin D signaling switches off pro-inflammatory programs of T[SUB]H[/SUB]1 cells

• Daniel Chauss,
• Tilo Freiwald,
• …
• Behdad Afzali

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Nature Immunology (2021)Cite this article

Abstract


The molecular mechanisms governing orderly shutdown and retraction of CD4[SUP]+[/SUP] type 1 helper T (T[SUB]H[/SUB]1) cell responses remain poorly understood. Here we show that complement triggers contraction of T[SUB]H[/SUB]1 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[SUP]+[/SUP] T[SUB]H[/SUB]1 cells to suppressive interleukin-10[SUP]+[/SUP] cells. This process was primed by dynamic changes in the epigenetic landscape of CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cells of patients with COVID-19 were T[SUB]H[/SUB]1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.

https://www.nature.com/articles/s41590-021-01080-3#Sec2

 

[sharon sanders]

snip

The study suggests that vitamin D could be a therapeutic option for COVID-19 thanks to its role in hyper-inflammation.

“This study reveals a potentially unique role that vitamin D plays in the activation of T-cell functions that regulate inflammation in COVID-19, and understanding these regulatory pathways may provide information that will lead to the development of novel therapies for the treatment of acute COVID-19,” said Dr. Alcendor.

Dr. Donald J. Alcendor, associate professor of pathology, microbiology, and immunology at Vanderbilt University School of Medicine, said the study offered clues to a possible mechanism that will need validation on a larger scale.

“There is widespread belief among the general public that taking megadoses of vitamin D can protect you prior to or following testing positive for COVID-19. The science supporting these claims is still evolving and will require a large-scale control clinical trial going forward. Even more, the mechanism for how vitamin D affects COVID-19 is still unknown,” he said.

Dr. Alcendor said that even though vitamin D is known to have immune-modulatory functions, it does not justify its use as a protective measure against COVID-19 infection, especially if one ignores COVID-19 mitigation practices.

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