More MS news articles for Mar 2002

Increased Severity of Experimental Allergic Encephalomyelitis in lyn(-/-) Mice in the Absence of Elevated Proinflammatory Cytokine Response in the Central Nervous System

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11884485&dopt=Abstract

J Immunol 2002 Mar 15;168(6):3105-12
Du C, Sriram S.
Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN 37212.

lyn, a member of the src kinase family, is an important signaling molecule in B cells. lyn(-/-) mice display hyperactive B-1 cells and IgM hyperglobulinemia.

The role of lyn on T cell function and development of Th1-mediated inflammatory disease is not known.

Therefore, we examined the effect of disruption of the lyn gene on the development of experimental allergic encephalomyelitis (EAE), a well-established Th1-mediated autoimmune disease.

Following immunization with myelin oligodendrocyte protein (MOG) p35-55, lyn(-/-) mice had higher clinical and pathological severity scores of EAE when compared with wild type (WT).

The increase in the severity of EAE in lyn(-/-) mice was not associated with a commensurate increase in the production of proinflammatory cytokines in the CNS. lyn(-/-) mice with EAE showed elevation in serum anti-IgM MOG Ab levels over that seen in WT mice, along with a modest increase in the mRNA levels of complement C5 and its receptor, C5aR, in the spinal cord.

Transfer of serum from MOG-immunized lyn(-/-) mice worsened EAE in WT mice, suggesting a pathogenic role for anti-MOG IgM Abs in EAE.

These observations underscore the potential role of lyn in regulation of Th1-mediated disease and the role of autoantibodies and complement in the development of EAE.