Androgen-mediated regulation of ILC2: towards a better understanding of sex differences in immunity
If the influence of sex on immunity is now increasingly recognised, the underlying mechanisms are still ill-defined. Females have a clear immunological advantage over males which is reflected in an increased ability to fight helminthic infections, while they experience more frequent and severe asthma. Both pathologies are associated with type 2 immune responses, which help expel parasites but also trigger allergic reactions. Group 2 innate lymphoid cells (ILC2s) are essential effectors cells of type 2 immunity, with natural ILC2s (nILC2) being key drivers of asthma, while the more recently identified inflammatory ILC2 subtype (iILC2) being involved in parasitic infection control. Our pioneering research has demonstrated that androgens inhibit the activation and expansion of nILC2s, offering males protection against allergen-induced lung inflammation. The aim of this proposal, based on solid preliminary data, will be to unravel mechanisms by which androgens regulate nILC2s and to explore whether these findings extend to human ILC2s. In parallel, we will evaluate whether inflammatory ILC2s are controlled by sexual hormones, which will help to elucidate mechanisms that govern sex bias in parasitic infections. This project is part of a new and expanding field of research aiming at considering sex as an essential biological factor and at better understanding how sex biological factors impact physiology.
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Imported from OpenAIRE Germany | Grant ANR-25-CE15-2589.
Open sourceOverview
Grant agreement ANR-25-CE15-2589 | SexiILC
Open sourceIf the influence of sex on immunity is now increasingly recognised, the underlying mechanisms are still ill-defined. Females have a clear immunological advantage over males which is reflected in an increased ability to fight helminthic infections, while they experience more frequent and severe asthma. Both pathologies are associated with type 2 immune responses, which help expel parasites but also trigger allergic reactions. Group 2 innate lymphoid cells (ILC2s) are essential effectors cells of type 2 immunity, with natural ILC2s (nILC2) being key drivers of asthma, while the more recently identified inflammatory ILC2 subtype (iILC2) being involved in parasitic infection control. Our pioneering research has demonstrated that androgens inhibit the activation and expansion of nILC2s, offering males protection against allergen-induced lung inflammation. The aim of this proposal, based on solid preliminary data, will be to unravel mechanisms by which androgens regulate nILC2s and to explore whether these findings extend to human ILC2s. In parallel, we will evaluate whether inflammatory ILC2s are controlled by sexual hormones, which will help to elucidate mechanisms that govern sex bias in parasitic infections. This project is part of a new and expanding field of research aiming at considering sex as an essential biological factor and at better understanding how sex biological factors impact physiology.