In industrialized countries, the incidence of autoimmune diseases continues to rise and currently affects 5 to 8% of the population. This family comprises more than 80 distinct chronic conditions, including systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis, and myasthenia gravis. These pathologies affect women far more frequently than men, to the extent that they rank among the leading causes of morbidity in women. They result from a breakdown of immune tolerance processes, which are normally established in immune tissues such as the thymus and bone marrow in order to identify and eliminate autoreactive T lymphocytes. When this control fails, the adaptive immune response spirals out of control and may target the body's own constituents.
This review seeks to understand why women are particularly susceptible and what role the environment plays in triggering the disease. The development of an autoimmune reaction requires the convergence of several factors: an intrinsic predisposition (genetic polymorphisms such as major histocompatibility complex genotypes, sex hormones, abnormalities in X-chromosome inactivation), failures of immune regulatory mechanisms (deficiencies in regulatory T lymphocytes and type 17 helper T lymphocytes), and exposure to inducing environmental factors. Epidemiological studies and observations in monozygotic twins, who show incomplete concordance for these diseases, confirm the weight of this extrinsic component, which notably includes viruses, the microbiota, and pollution.
The authors focus their analysis on estrogen, the female sex hormone implicated in the increased susceptibility of women, and on environmentally present molecules endowed with endocrine-disrupting properties. Some of the cellular effects of these compounds, including polycyclic aromatic hydrocarbons and the dioxin TCDD, may be mediated by the aryl hydrocarbon receptor (AhR). The review successively examines the action of these molecules on the homeostasis of thymic cells, on the intrinsic factors of immune tolerance (transcription factors, epigenetic marks), and on its extrinsic factors (microbiota, susceptibility to viruses).
By bringing together these different levels of analysis, this work highlights the joint contribution of estrogen and endocrine disruptors to the dysregulation of the mechanisms underlying the development of autoimmune diseases. The value of this approach lies in explicitly linking a hormonal predisposition and environmental exposures within a single explanatory framework, placing the thymus and tolerance processes at the center of the discussion.