Commensal regulation of T cell survival through Erdr1.
Gut Microbes
; 9(5): 458-464, 2018.
Article
em En
| MEDLINE
| ID: mdl-29543554
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Proteínas Supressoras de Tumor
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Encefalomielite Autoimune Experimental
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Microbioma Gastrointestinal
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Gut Microbes
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos