IFNG-producing self-reactive CD4+ T cells induce autoimmune adrenalitis in a mouse model of Addison's disease.

Andreyeva, Arina; Michalik, Juraj; Niederlova, Veronika; Cimermanova, Veronika; Drobek, Ales; Sedlacek, Radislav; Prochazka, Jan; Labaj, Juraj et al. · JCI Insight · 2026

basic_science · Level V

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Abstract

Autoimmune Addison's disease (AD) is a rare but life-threatening disorder caused by immune-mediated destruction of the adrenal cortex, and progress in therapy has been limited by insufficient mechanistic insight. Here, we establish a model of Experimental Autoimmune Adrenalitis (EAA) that recapitulates key features of AD and reveals sex-dependent differences in disease manifestation within the model. Immunization with peptides derived from the adrenal self-antigen CYP11A1 induces corticosterone insufficiency. We show that autoimmune adrenalitis is driven by IFNG produced by self-reactive CD4+ T cells, promoting granulomatous inflammation in the adrenal cortex. Together, these findings identify IFNG as a central effector of autoimmune adrenalitis and suggest that targeting the IFNG pathway may represent a potential therapeutic strategy for AD.