Sex hormones are major regulators of skin immunity. Pregnancy represents a unique physiological state of profound hormonal remodeling. In late pregnancy, maternal levels of estrogens, progesterone, and other hormones increase dramatically, offering an unparalleled model to study the impact of sex hormones on skin immunity. Hidradenitis suppurativa (HS) provides a clinically relevant model to examine how sex hormones modulate skin inflammation.

Sex hormones are major regulators of skin immunity. Recent work from Belkaid's laboratory in mice demonstrated that testosterone negatively regulated skin innate lymphoid cells (ILC2), leading to a reduction in dendritic cell accumulation and decreased activation in males, along with reduced tissue immunity. These findings highlight that sex-related differences in skin immunity emerge primarily after sexual maturation, driven by fluctuating hormone levels. However, whether these mechanisms are conserved in humans remains unknown.

Pregnancy represents a unique physiological state of profound hormonal remodeling. In late pregnancy, maternal levels of estrogens, progesterone, and other hormones increase dramatically, offering an unparalleled model to study the impact of sex hormones on skin immunity. Understanding maternal skin immunity is of particular importance, as the maternal immune system must balance tolerance to the fetus with protection against pathogens. Perturbation in this balance can have lasting effects on both maternal and child health. Faced with the dramatic increase in inflammatory and autoimmune disorders affecting children globally, understanding maternal immunity is of fundamental importance.

Hidradenitis suppurativa (HS) provides a clinically relevant disease model to examine how sex hormones modulate skin inflammation. HS is a chronic inflammatory skin disease with strong sex dimorphism: it affects predominantly women (70%) in Europe but is often more severe in men. In women, HS severity varies with the menstrual cycle and is frequently altered during pregnancy, suggesting a hormonal component in disease modulation. Yet, the mechanisms linking sex hormones, pregnancy, and skin immune responses in HS remain unexplored.

By systematically comparing men, non-pregnant women, and pregnant women, in both health and HS, this study will map immune cell populations in the skin and determine how sex hormones; testosterone, estrogens, and progesterone; shape cutaneous immunity at steady state and during inflammation.

Inclusion Criteria:

• Common criteria :
• Subject>18 years and <45 years,
• Written informed consent of the subject,
• Subject affiliated to the Assurance Maladie (French Health System) except Aide Médicale d'Etat (French State Medical Aid),
• Subject agrees that genomic analyses may be carried out on the samples
• Specific criteria :
• For pregnant women:Third trimester of pregnancy (between 29-37 weeks of amenorrhea).
• For HS subjects: Subject with hidradenitis suppurativa lesions at the sampling sites.

Exclusion Criteria:

• Common criteria :
• Subject immunocompromised,
• Subject under legal protection (guardianship or curatorship),
• Subject is unable to provide informed consent and to comply with the study requirements due to geographical, social, or psychiatric reasons,
• Subject in other research whose procedures may influence the immune system,
• Contraindication to any of medications listed in section 5.1 (antiseptic and local anesthetic used for biopsy(ies)),
• Subject whose health condition does not permit participation in study procedures.
• Specific criteria :
• For no HS subjects : Scarred skin at the biopsy site, Subject with pre-existing and/or still active inflammatory skin conditions, Subject experiencing early menopause (women) or andropause (men).

As part of this study, adults (pregnant women, non-pregnant women, and men), healthy (not affected by HS) and affected by HS, will be recruited.