Identification of variant isoforms of CD44 and their functions in murine immune cells (87.6)

Abstract

Abstract CD44 is known to be implicated in a variety of immunological processes such as T cell migration, activation and differentiation. CD44 comprises a standard form and a family of isoforms that vary by their degree of post-translational modifications and due to alternative splicing of their primary amino acid sequence encoded by up to 10 variant exons. The isoforms actually determine the differential functions of CD44 in various types of immune cells and immune responses. Upon activation, lymphocytes transiently express certain CD44 splice variants. However, the precise nature of CD44 variant isoforms expressed by various cells types of the immune system has not been studied thus far. In this report, we screened variant exons from exon 1 to 10 using Southern blot hybridization and identified CD44 isoforms on CD4, CD8, FoxP3+ Treg and dendritic cells, either naïve or activated with SRBC, OVA, LPS, anti-CD3 plus anti-CD28, or IL-2 respectively. The results showed distinct isoforms for each cell type that also varied based on naïve or activated status. In experimental autoimmune encephalomyelitis (EAE), targeted deletion of full CD44 sequence prevented EAE whereas sole deletion of variant 7 induced a progressive and non-remitting type of EAE. Our study, has for the first time, identified the unique CD44 isoforms expressed on murine CD4, CD8, Treg and dendritic cells and shown the differential role of CD44 variant isoforms in the regulation of autoimmune disease.