Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.

ABSTRACT: RasGRP1 is a Ras guanine nucleotide exchange factor, and an essential regulator of lymphocyte receptor signaling. In mice, Rasgrp1 deletion results in defective T lymphocyte development. RASGRP1-deficient patients suffer from immune deficiency, and the RASGRP1 gene has been linked to autoimmunity. However, how RasGRP1 levels are regulated, and if RasGRP1 dosage alterations contribute to autoimmunity remains unknown. We demonstrate that diminished Rasgrp1 expression caused defective T lymphocyte selection in C57BL/6 mice, and that the severity of inflammatory disease inversely correlates with Rasgrp1 expression levels. In patients with autoimmunity, active inflammation correlated with decreased RASGRP1 levels in CD4⁺ T cells. By analyzing H3K27 acetylation profiles in human T cel

SUBMITTER: Baars MJD 

PROVIDER: S-EPMC7894479 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature