Guselkumab binding to CD64⁺ IL-23-producing myeloid cells enhances potency for neutralizing IL-23 signaling.

ABSTRACT: IL-23 is implicated in the pathogenesis of immune-mediated inflammatory diseases, and myeloid cells that express Fc gamma receptor 1 (FcγRI or CD64) on their surface have been recently identified as a primary source of IL-23 in inflamed tissue. Our complementary analyses of transcriptomic datasets from psoriasis and IBD showed increased expression of CD64 and IL-23 transcripts in inflamed tissue, and greater abundance of cell types with co-expression of CD64 and IL-23. These findings led us to explore potential implications of CD64 binding on the function of IL-23-targeting monoclonal antibodies (mAbs). Guselkumab and risankizumab are mAbs that target the IL-23p19 subunit. Guselkumab has a native Fc domain while risankizumab contains mutations that diminish binding to FcγRs. In flow cytome

SUBMITTER: Sachen KL 

PROVIDER: S-EPMC11937023 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature