CD44 variant expression differs on CD4 T cell subsets and correlates with response to hyaluronic acid 3860

Abstract Description CD44, a transmembrane glycoprotein, is widely recognized as an activation marker of T cells and crucially mediates adaptive immune responses. It exists in standard form (CD44s) or several variant isoforms (CD44v) from alternative splicing of its coding region, which contains ten constant and ten variable exons. This receptor primarily binds hyaluronic acid (HA) to facilitate T cell trafficking, adhesion, and activation. The effect of HA on CD44-mediated signaling vary depending on HA’s molecular weight and is thought to lead to distinct T cell outcomes: low molecular weight HA (LMW-HA) may promote inflammatory and immunogenic responses, while high molecular weight HA (HMW-HA) could induce anti-inflammatory effects. Despite the documented variations in plasma HA across different diseases, the expression and role of CD44v on CD4 T cell responses is poorly understood. We tested if the expression of CD44v on CD4 T cells differs by to subset. Using a primer set that targets exon 5 of the constant region of CD44 with reverse primers for each of the ten variant exons, we compared the expression of CD44 variants in CD4 T cells. We demonstrated that CD44v expression exhibited different profiles among Th1, natural Tregs, and inducible Tregs. To determine how HA exposure may influence CD44 mediated functions, we treated Th1 and iTregs with HA. While exposure to LMW-HA in Th1 cells resulted in an increase in Tbet and interferon-γ, exposure of iTregs to HMW HA promoted IL-10 secretion. Funding Sources F31 (NIH F31HL172638-01) Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)