Cytosolic phospholipase A2α–deficient mice are resistant to experimental autoimmune encephalomyelitis

• DOI: 10.1084/jem.20050665
• Publication Date: 2005-09-19T19:18:07Z
• Authors: Suzana Marusic; Michael W. Leach; Jeffrey W. Pelker; Mihai L. Azoitei; Naonori Uozumi; Junqing Cui; Marina W.H. Shen; Charlene M. DeClercq; Joy S. Miyashiro; Brenda A. Carito; Paresh Thakker; David L. Simmons; John P. Leonard; Takao Shimizu; James D. Clark
• Keywords: Mice, Knockout; 0303 health sciences; Encephalomyelitis, Autoimmune, Experimental; Group IV Phospholipases A2; Cell Differentiation; Th1 Cells; Interleukin-12; Article; Immunity, Innate; Phospholipases A; Immunophenotyping; 3. Good health; Mice, Inbred C57BL; Mice; Myelin-Associated Glycoprotein; Phospholipases A2; 03 medical and health sciences; Cytosol; Spinal Cord; Animals; Female; Myelin-Oligodendrocyte Glycoprotein; Myelin Proteins

Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is a model of human multiple sclerosis. Cytosolic phospholipase A2α (cPLA2α), which initiates production of prostaglandins, leukotrienes, and platelet-activating factor, is present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well as an adoptive transfer model, we showed that cPLA2α−/− mice are resistant to EAE. Histologic examination of the CNS from MOG-immunized mice revealed extensive inflammatory lesions in the cPLA2α+/− mice, whereas the lesions in cPLA2α−/− mice were reduced greatly or completely absent. MOG-specific T cells generated from WT mice induced less severe EAE in cPLA2α−/− mice compared with cPLA2α+/− mice, which indicates that cPLA2α plays a role in the effector phase of EAE. Additionally, MOG-specific T cells from cPLA2α−/− mice, transferred into WT mice, induced EAE with delayed onset and lower severity compared with EAE that was induced by control cells; this indicates that cPLA2α also plays a role in the induction phase of EAE. MOG-specific T cells from cPLA2α−/− mice were deficient in production of Th1-type cytokines. Consistent with this deficiency, in vivo administration of IL-12 rendered cPLA2α−/− mice susceptible to EAE. Our data indicate that cPLA2α plays an important role in EAE development and facilitates differentiation of T cells toward the Th1 phenotype.