datadragon
Senior Member
- Messages
- 397
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- USA
it has been hypothesized that the reason why women are more prone than men to develop T-cell autoimmune diseases is because they exhibit more robust Th1 adaptive immunity. Our finding that naïve CD4+ T cells of women produced higher levels of IFNγ and tended to proliferate more than male T cells provides direct support for this notion. PPARα has a sex-specific role in the negative regulation of T-cell IFNγ production. Here, we report the observation that naïve cluster of differentiation (CD)4+ T cells from women are intrinsically geared to proliferate and produce higher levels of IFNγ and lower levels of IL-17A compared with male T cells. This sex difference in Th biology was also apparent in Swiss/Jackson Laboratory (SJL) mice. Furthermore, we found that the female Th1 bias was associated with a higher expression of PPARα by male activated T cells and higher expression of the immune-expressed PPARγ variant PPARγ1 by activated female T cells.
Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way
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.
https://www.pnas.org/doi/10.1073/pnas.1118458109
Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way
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.
https://www.pnas.org/doi/10.1073/pnas.1118458109
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