| First Author | Zhang MA | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 24 | Pages | 9505-10 |
| PubMed ID | 22647601 | Mgi Jnum | J:185518 |
| Mgi Id | MGI:5429104 | Doi | 10.1073/pnas.1118458109 |
| Citation | Zhang MA, et al. (2012) Peroxisome proliferator-activated receptor (PPAR)alpha and -gamma regulate IFNgamma and IL-17A production by human T cells in a sex-specific way. Proc Natl Acad Sci U S A 109(24):9505-10 |
| abstractText | 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 naive 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 IFNgamma 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)alpha and PPARgamma. Androgens increased PPARalpha and decreased PPARgamma expression by human CD4(+) T cells. PPARalpha siRNA-mediated knockdown had the effect of increasing IFNgamma by male CD4(+) T cells, while transfection of CD4(+) T cells with PPARgamma 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 IFNgamma and IL-17A that may be driven by expressions of PPARalpha and PPARgamma. |
