BHLHE40 Regulates IL-10 and IFN- γ Production in T Cells but Does Not Interfere With Human Type 1 Regulatory T Cell Differentiation.

Autor:	Uyeda MJ; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States.; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Freeborn RA; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Cieniewicz B; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Romano R; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Chen PP; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Liu JM; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Thomas B; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States.; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Lee E; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States.; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Cepika AM; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States., Bacchetta R; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States.; Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, United States., Roncarolo MG; Department of Pediatrics, Division of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States.; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States.; Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Jul 07; Vol. 12, pp. 683680. Date of Electronic Publication: 2021 Jul 07 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.683680
Abstrakt:	Type 1 regulatory T (Tr1) cells are subset of peripherally induced antigen-specific regulatory T cells. IL-10 signaling has been shown to be indispensable for polarization and function of Tr1 cells. However, the transcriptional machinery underlying human Tr1 cell differentiation and function is not yet elucidated. To this end, we performed RNA sequencing on ex vivo human CD49b + LAG3 + Tr1 cells. We identified the transcription factor, BHLHE40, to be highly expressed in Tr1 cells. Even though Tr1 cells characteristically produce high levels of IL-10, we found that BHLHE40 represses IL-10 and increases IFN-γ secretion in naïve CD4 + T cells. Through CRISPR/Cas9-mediated knockout, we determined that IL10 significantly increased in the sgBHLHE40-edited cells and BHLHE40 is dispensable for naïve CD4 + T cells to differentiate into Tr1 cells in vitro . Interestingly, BHLHE40 overexpression induces the surface expression of CD49b and LAG3, co-expressed surface molecules attributed to Tr1 cells, but promotes IFN-γ production. Our findings uncover a novel mechanism whereby BHLHE40 acts as a regulator of IL-10 and IFN-γ in human CD4 + T cells. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Uyeda, Freeborn, Cieniewicz, Romano, Chen, Liu, Thomas, Lee, Cepika, Bacchetta and Roncarolo.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu