ADAM10 is a novel sheddase of Inducible Costimulatory Ligand (ICOSL).

• DOI: 10.4049/jimmunol.198.supp.195.18
• Publication Date: 2023-01-01T10:50:30Z
• Authors: Andrea Luker; Joseph Cornelius ...; Daniel Conrad
• Keywords: ADAM10; Internalization

Abstract ICOSL is an important co-stimulatory molecule involved in the development of TH2 responses through germinal center reactions. Although not well defined, regulation known to occur its interaction with ICOS. Evidence suggests surface expression levels are regulated by a catabolic event, and internalization. Here we confirm that mediated metalloproteinase ADAM10. Cleavage recombinant results amino-terminal fragment approximately 3kDa, which blocked ADAM10-specific inhibitor. Recombinant cell-based cleavage assays suggest ADAM17 can also cleave ICOSL. In vivo, observed ten-fold increase ADAM10B−/− mice compared wildtype, phenomenon was absent ADAM17B−/− mice. This ADAM10 primary physiological sheddase ICOSL, while may serve as secondary sheddase. Additionally, develop significantly diminished T follicular helper (TFH) cell population response NP-KLH/alum immunization. Together, these data provide insight into regulatory mechanism between ICOS/ICOSL be potential therapeutic target for attenuating antibody driven diseases.