Immunopathology and Immunotherapy of Inflammatory Skin Diseases

Pathophysiology of and immunotherapeutic agents for psoriasis. External environmental stress and trauma is a possible trigger of psoriasis, especially in individuals with genetic susceptibilities (e.g., PSORS1). This leads to the release of CCL20, CXCL8, and CXCL1, stimulating CCR6+IL-17+ lymphocytes, neutrophils, and IL-23+CD14+ DCs, respectively. Release of IL-17A and IL-17F via IL-17-producing cells (Th17, Tc17, and ILC3) results in the activation of the IL-17RA/IL-17RC complex in keratinocytes, further feeding the inflammatory response. Production of IL-22 by ILC3 accelerates hyperproliferation of keratinocytes. DCs induce cytokines like IL-1β, TNF-α, and IL-23. IL-17-producing cells are stimulated by IL-23 through the JAK2/TYK2-STAT3 pathway. Ustekinumab targets the p40 subunit shared by IL-12 and IL-23, and guselkumab and risankizumab inhibit the p19 subunit of IL-23. Secukinumab and ixekizumab are inhibitors of IL-17A. Bimekizumab is a monoclonal antibody targeting IL-17A and IL-17F. Brodalumab is an inhibitor of IL-17RA. With respect to JAK signaling, deucravacitinib acts to inhibit TYK2, and brepocitinib inhibits TYK2 and JAK1 simultaneously.

Publication

Immunopathology and Immunotherapy of Inflammatory Skin Diseases. (2022) Ahreum Song, et al. Immune Netw. 2022 Feb;22(1):e7. Figure: F1. Homo sapiens

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