Coordination Funds

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Our immune system defends us from pathogens and removes abnormal cells that potentially lead to malignancies. Optimal immunological homeostasis is achieved when the threat is removed with the highest efficiency whilst avoiding collateral tissue damage for the host. Increasing scientific evidence suggests that this immunological balance is different between women and men. It has been shown that women mount stronger immune responses against pathogens, leading to more rapid control or clearance of infections. Women also develop stronger immunity in response to vaccinations, and exhibit stronger immune responses against some malignancies. Enhanced immune responsiveness in females, however, comes at a cost, including aggravated tissue damage, persistent inflammation and significantly higher incidences of autoimmune diseases. These sex-specific differences are not restricted to adults, as already boys have an increased risk for infections early in life, while girls develop a greater risk for atopic diseases around puberty. Despite these well-established differences in clinical manifestations of infectious and autoimmune diseases between females and males, the underlying biological mechanisms have not been systematically examined. The overall goal of the RU 5068 “sex differences in immunity” is to systematically investigate mechanisms underlying sex-specific differences in immunity against self and foreign, focusing on human diseases for which differences in prevalence and manifestations exist between women and men. The RU 5068 will assess the principal hypothesis that common biological pathways are responsible for sex-based differences, and will determine the mechanisms by which (i) sex steroid hormones and (ii) X chromosomal genes modulate immunological pathways responsible for sex differences in immunity. Our RU brings together basic and clinician scientists that are leaders in their respective fields of specific research in the areas of autoimmunity, infectious diseases and malignancies, and have a strong research focus on sex-specific differences in immunity. One of the strengths of the RU 5068 is that consequences of sex hormones and X chromosomal genes on immunity are investigated in different models assessing immunity to foreign or self. The proposed work program will combine use of human samples to investigate immunological differences, and mouse models to identify underlying mechanisms and to test interventions. The understanding of the mechanisms underlying sex differences in immunity will pave the way for novel treatment strategies for infectious and immune-mediated diseases that take the sex of the affected individual into account.