Colloque de rentrée 2024 - Genre et Sciences : Défenses immunitaires et dimorphisme sexuel

Session 3 : Science biologique et génomique, juridique

Yasmine Belkaid

Directrice générale de l'Institut Pasteur

Séance animée par Vinciane Pirenne-Delforge

Résumé

The immune system serves as a potent rheostat of host physiology, a fundamental function that requires specialized regulation across tissues, age and biological sex. Such tailored control also contributes to differences in disease manifestations. Notably, sex bias in host immunity is believed to account for differences in the incidence, tropism and severity of diseases between males and females. Clinical and experimental work revealed that females tend to develop stronger responses to infections and vaccines, and have a greater incidence of autoimmune disorders than males. As an illustration of this phenomenon, sex differences in infection outcomes were recently highlighted in the context of the SARS-CoV-2 pandemic, with enhanced risk for severe infection and lethality in men compared to women. Differential susceptibility to infections and inflammatory disorders has been, at least in part, attributed to heightened innate and adaptive immune potency in females than males (3, 4). While several mechanisms have been proposed to account for this phenomenon, our understanding of the key players involved in shaping sex-specific immunity remains surprisingly sparse. Sexual dimorphism can result from sex chromosome and/or hormonal control of host physiology. Notably, both androgens and estrogens have been shown to have the capacity to directly impact the function of various immune cells. Sexual bias in host immunity is of particular importance in barrier tissues that are primary targets of infections, injury and chronic inflammatory disorders. Indeed, sexual dimorphism has long been recognized in the context of various barrier tissue inflammatory disorders such as asthma, atopic dermatitis and Sjögren's syndrome. Collectively, biological sex has broadly been associated with differences in the intensity and tropism of numerous disorders. How constitutive wiring of barrier tissues in males versus females predicts disease outcomes remains largely unclear, but emerging evidence supports the idea that each tissue may be differentially impacted by biological sex. For instance, comparison of 44 human tissues revealed tissue-specific differences in the number of genes differentially regulated between men and women, with the skin notably displaying the highest number of sex−biased genes. We uncovered a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. This recent work reveals an androgen-ILC2-DC axis in controlling sexual immune dimorphism.

Yasmine Belkaid

Pr Yasmine Belkaid is the President of the Institut Pasteur (Paris) and the head of the Metaorganism Immunity laboratory at the Institut Pasteur. She obtained her Master in Biochemistry at the University of Science and Technology Houari Boumediene in Algiers, Algeria and her PhD from the Institut Pasteur in France. Following a postdoctoral fellowship at the National Institute of health (Bethesda) on immune regulation during infection, she started her research program at the Children's Hospital Research Foundation in Cincinnati. In 2005, she joined the National Institute of Allergy and Infectious Diseases (NIAID) where she served as department chair of the Laboratory of Host Immunity and Microbiome, Director of the trans-NIH Center for Human immunology and founder and Director of the NIAID Microbiome program prior to joining the Institut Pasteur in 2024. Her work explores fundamental mechanisms that regulate tissue homeostasis and host immune responses and uncovered key roles for the microbiota and dietary factors in the control of immunity and protection to pathogens. Her work also explores the role of the immune system in organismal remodeling and the impact of infections on maternal child DYAD. Dr Belkaid is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the National Academy of Medicine and recipient of numerous awards including the Lurie Prize in Biomedical Sciences, the Emil von Behring Prize, the Sanofi-Institut Pasteur Award, the Robert Koch Award and the AAI Excellence in Mentoring Award.