Controlling Leukocyte Migration in Autoimmune Encephalomyelitis by the TIPE Family of Phospholipid Transfer Proteins.

Abstract

Abstract Leukocyte migration is essential for immune organ development, immune surveillance, and autoimmune diseases. A common pathogenic mechanism of multiple sclerosis (MS) is the infiltration of the central nervous system (CNS) by activated leukocytes. The CNS is an immunologically privileged site to which access of circulating leukocytes is tightly controlled by the blood-brain barrier (BBB). How leukocytes cross the BBB during MS is not well understood. We report here that members of the TNFAIP8 (TNF-alpha-induced protein 8-like) family control leukocyte migration during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Using single or double TIPE deficient mice generated in our lab, we found that TNFAIP8 and TIPE2 were required for the development of EAE. Although TIPE2-deficient myelin-specific TH1 and TH17 cells were hypersensitive to myelin antigens, they had an intrinsic defect in migration into CNS. Further analysis indicated that TIPE family members affected cell polarization. The molecular mechanisms underlying these abnormalities are under investigation. These findings establish that TIPE family plays important roles in EAE and could be a potential therapeutic target for treating MS. Supported by NIH grant.