Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41124250.
- Also identified by DOI 10.1126/sciadv.adx0637 and PMC identifier 12542932.
- Licence recorded as CC BY-NC.
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Abstract
Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T<sub>H</sub>17) 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<sub>H</sub>2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by T<sub>H</sub>2/T<sub>H</sub>17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined T<sub>H</sub>2/T<sub>H</sub>17 stimulation. Lesional T cells from EczPso-but not from eczema or classical plaque Pso-proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.
Medical subject headings
- Psoriasis
- Serpins
- Autoantigens