Commensal regulation of T cell survival through Erdr1. (3rd September 2018)

• Record Type: Journal Article
• Authors: Weis, Allison M.; Soto, Raymond; Round, June L.
• Is Part Of: Gut microbes. Volume 9:Isuse 5(2018)
• Page Start: 458
• Page End: 464
• Publication Date: 2018-09-03
• Subjects: Erdr1 -- TLRs -- autoimmunity -- T cells -- microbiota -- Host-pathogen interactions; Gastrointestinal system -- Microbiology -- Periodicals; Microbiology -- Periodicals; Intestine, Small -- Periodicals; 616.3
• DOI: 10.1080/19490976.2018.1441662
• Languages: English
• ISSNs: 1949-0984

Abstract

ABSTRACT: The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway. Suppression of Erdr1 leads to survival of autoreactive T cells and exacerbated autoimmune disease in the EAE model, and overexpression of Erdr1 results in lessened disease. This novel T cell apoptotic factor has implications for autoimmunity, cancer biology, and invasive pathogens and thus represents a novel therapeutic target in disease.