Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way.
Proc Natl Acad Sci U S A
; 109(24): 9505-10, 2012 Jun 12.
Article
em En
| MEDLINE
| ID: mdl-22647601
ABSTRACT
Women develop certain autoimmune diseases more often than men. It has been hypothesized that this may relate to the development of more robust T-helper (Th)1 responses in women. To test whether women exhibit a Th1 bias, we isolated naïve cluster of differentiation (CD)4(+) T cells from peripheral blood of healthy women and men and measured the proliferation and cytokine production by these cells in response to submaximal amounts of anti-CD3 and anti-CD28. We observed that CD4(+) T cells from women produced higher levels of IFNγ as well as tended to proliferate more than male CD4(+) T cells. Intriguingly, male CD4(+) T cells instead had a predilection toward IL-17A production. This sex dichotomy in Th cytokine production was found to be even more striking in the Swiss/Jackson Laboratory (SJL) mouse. Studies in mice and humans indicated that the sexual dimorphism in Th1 and Th17 cytokine production was dependent on the androgen status and the T-cell expression of peroxisome proliferator activated receptor (PPAR)α and PPARγ. Androgens increased PPARα and decreased PPARγ expression by human CD4(+) T cells. PPARα siRNA-mediated knockdown had the effect of increasing IFNγ by male CD4(+) T cells, while transfection of CD4(+) T cells with PPARγ siRNAs increased IL-17A production uniquely by female T cells. Together, our observations indicate that human T cells exhibit a sex difference in the production of IFNγ and IL-17A that may be driven by expressions of PPARα and PPARγ.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Linfócitos T CD4-Positivos
/
Interferon gama
/
Interleucina-17
/
PPAR alfa
/
PPAR gama
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article