CD44 v5 domain inhibition represses the polarization of Th2 cells by interfering with the IL-4/IL-4R signaling pathway.

The balance between Th1 and Th2 cells is critical for both innate and acquired immune reactions. But the precise mechanisms of T helper cells differentiations are still unclear. As an important T cell activation molecular, CD44 participates in the Th1 and Th2 differentiation. We demonstrated that CD44 variant exon-v5 is highly expressed by induced human Th2 cells. In order to investigate the role of CD44v5 domain in Th2 cell differentiation, we treated human CD4+ T cells with CD44v5 antibody and observed that the levels of pSTAT6 and GATA3 and the secretion of IL-4 were significantly decreased after the treatment. We also further found that the inhibition of Th2 differentiation was caused by the IL-4Rα degradation, CD44v5 domain co-localized with IL-4Rα on cell surface, the degradation of IL-4Rα increased after CD44v5 blocking or ablating. Our results indicated that CD44v5 antibody treatment interrupted the interaction between CD44v5 and IL-4Rα, but the CD44v5 domain blockage would not spoil the co-localization between IL4R expression and TCR and the immunological synapse formation, similar results were also found in CD44v5 deficient CD4+ T cells. In conclusion, we revealed the function of CD44v5 domain in Th2 cell differentiation, blocking or ablating CD44v5 domain could accelerate IL-4Rα degradation and then induce the Th2 cell inhibition.