The immune network, and the host of of its modulators, represent -alongside the central nervous system- the most complex entity in human biology, which makes the full contextualization of immune responses in health an disase one of the hardest tasks of research. This picture is further complicated by sex-based differences: indeed it is a well-known fact that males and females can differ significanlty when it comes to immune processes, as well as to the prevalence of autoimmune diseases, with women being more prone to develop conditions such as rheumatoid arthritis, lupus erythematosus and multiple sclerosis (MS). An important culprit of this difference has been found in the ormonal differences that lead to immune alterations (e.g. cytokine expression, generation of pathogenetic phenotypes of immuno cells), which, in turn, are thought to trigger the pathogenesis of autoimmune conditions. In this rather vast puzzle, a research group from Chicago School of Medicine might have recently found a new piece that helped clarifying how ormonal and immune differences between sexes have an impact in MS susceptibility and development.
Russi and colleagues, started by a previous evidence that male mice that were resistant to experimental autoimmune encephalomyelitis (EAE, i.e. MS mouse model) had a tendency to accumulate, in CNS and draining lymph nodes, type 2 innate lymphoid cells (ILC2) that were able to mount a protective - non-pathogenetic - th2 anti-myelin response; interestingly, mice lacking ILC2 and, curiously, mast cells developed more robust EAE. They found that protective ILC2 accumulate in higher percentages in the lymphnodes of male mice that underwent EAE induction, in respect with females. This difference seemed to depend on the differential expression, between males and females, of mast cell-derived IL-33 -an ILC2 expander cytokine- which in turn is driven by testosterone. Lower testosterone levels might play an important part in this endocrine-immune axis and account, at least in part, for higher MS prevalence in female