PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation.
Blood
; 113(6): 1268-77, 2009 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-18945965
ABSTRACT
The identification of novel factors regulating human T helper (Th)-cell differentiation into functionally distinct Th1 and Th2 subsets is important for understanding the mechanisms behind human autoimmune and allergic diseases. We have identified a protein of relevant evolutionary and lymphoid interest (PRELI), a novel protein that induces oxidative stress and a mitochondrial apoptosis pathway in human primary Th cells. We also demonstrated that PRELI inhibits Th2-cell development and down-regulates signal transducer and activator of transcription 6 (STAT6), a key transcription factor driving Th2 differentiation. Our data suggest that calpain, an oxidative stress-induced cysteine protease, is involved in the PRELI-induced down-regulation of STAT6. Moreover, we observed that a strong T-cell receptor (TCR) stimulus induces expression of PRELI and inhibits Th2 development. Our results suggest that PRELI is involved in a mechanism wherein the strength of the TCR stimulus influences the polarization of Th cells. This study identifies PRELI as a novel factor influencing the human primary Th-cell death and differentiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Apoptose
/
Células Th1
/
Fator de Transcrição STAT6
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Newborn
Idioma:
En
Revista:
Blood
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Finlândia