Deconstructing the sex bias in allergy and autoimmunity: From sex hormones and beyond

Abstract

Men and women differ in their susceptibility to develop autoimmunity and allergy but also in their capacity to cope with infections. Mechanisms responsible for this sexual dimorphism are still poorly documented and probably multifactorial. This review discusses the recent development in our understanding of the cell-intrinsic actions of biological factors linked to sex, sex hormones and sex chromosome complement, on immune cells, which may account for the sex differences in the enhanced susceptibility of women to develop immunological disorders, such as allergic asthma or systemic lupus erythematosus (SLE). We choose to more specifically discuss the impact of sex hormones on the development and function of immune cell populations directly involved in type-2 immunity, and the role of the X-linked Toll like receptor 7 (TLR7) in anti-viral immunity and in SLE. We will also elaborate on the recent evidence demonstrating that TLR7 escapes from X chromosome inactivation in the immune cells of women, and how this may contribute to endow woman immune system with enhanced responsiveness to RNA-virus and susceptibility to SLE.

Keywords: Allergic asthma; Allergy and autoimmunity; Androgen receptor; Estrogen receptors; Group 2 innate lymphoid cells; Sex differences; Sex steroid hormones; Systemic lupus erythematosus; Toll-like receptor 7; X chromosome dosage.