Exploration of Immunology

Table 2. Sexual hormones regulate immune response and influence the sex-dimorphisms in ADs.

Hormone	General immunological effect	Mechanism of action	Impact on ADs	Sex-specific notes	References
Oestrogens	Immune-enhancing; promotes humoral responses	Increases B cell proliferation, class switching to IgG, Th2, and Treg responses; modulates Treg transcriptional programs	Can exacerbate antibody-mediated ADs such as SLE; may protect against Th1/Th17-driven ADs (e.g., MS, RA)	Effects depend on XX chromosomal background; levels fluctuate during puberty, pregnancy, menopause; high in pregnancy, induce Th2/Treg shift; low post-menopause, induce Th1/Th17 activation	[17, 44–46, 53]
Progesterone	Immunosuppressive; anti-inflammatory	Induces anti-inflammatory molecules; inhibits Th1 and Th17 pathways; modulates APC activation	Generally protective; reduces autoimmune activity	High during pregnancy, inducing symptom remission in some ADs	[44, 45]
Testosterone	Immunosuppressive; anti-inflammatory	Reduces pro-inflammatory cytokines (IL-1β, IL-6, TNF); increases IL-10; inhibits T cell proliferation; suppresses B cells and natural killer cytotoxicity	Protective against multiple ADs; a decline in ageing men (andropause) increases susceptibility	Effects observed in hypogonadal young men; therapeutic testosterone can restore male-like immune responses	[52–56]
Prolactin	Immune-enhancing	Promotes B cell activation and antibody production; upregulates costimulatory molecules on APCs; modulates Th1/Th2 cytokines	Can exacerbate autoimmune activity; hyperprolactinemia linked to onset/persistence of ADs	Levels fluctuate with reproductive states (pregnancy, postpartum)	[44, 46]

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ADs: autoimmune diseases; APCs: antigen-presenting cells; Ig: immunoglobulin; Th: T helper cell; Treg: regulatory T cell; SLE: systemic lupus erythematosus; MS: multiple sclerosis; RA: rheumatoid arthritis; APC: antigen presenting cell; IL: interleukin; TNF; tumour necrosis factor.

Declarations

Author contributions

AC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. GA: Writing—review & editing. AA: Writing—review & editing. RZ: Investigation, Writing—original draft, Writing—review & editing. GC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

Giuseppina Candore, who is the Editorial Board Member of Exploration of Immunology, had no involvement in the decision-making or review process of this manuscript. The other authors declare that they have no conflicts of interest.

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