Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis.

ABSTRACT: Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T_H17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a T_H2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by T_H2/T_H17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combi

SUBMITTER: Jargosch M 

PROVIDER: S-EPMC12542932 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature