B-cell very late antigen-4 deficiency reduces leukocyte recruitment and susceptibility to central nervous system autoimmunity.

Natalizumab, which binds very late antigen-4 (VLA-4), is a potent therapy for multiple sclerosis (MS). Studies have focused primarily upon its capacity to interfere with T-cell migration into the central nervous system (CNS). B cells are important in MS pathogenesis and express high levels of VLA-4. Here, we report that the selective inhibition of VLA-4 expression on B cells impedes CNS accumulation of B cells, and recruitment of Th17 cells and macrophages, and reduces susceptibility to experimental autoimmune encephalomyelitis. These results underscore the importance of B-cell VLA-4 expression in the pathogenesis of CNS autoimmunity and provide insight regarding mechanisms that may contribute to the benefit of natalizumab in MS, as well as candidate therapeutics that selectively target B cells.
AuthorsKlaus Lehmann-Horn, Sharon A Sagan, Claude C A Bernard, Raymond A Sobel, Scott S Zamvil
JournalAnnals of neurology (Ann Neurol) Vol. 77 Issue 5 Pg. 902-8 (May 2015) ISSN: 1531-8249 [Electronic] United States
PMID25712734 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
Chemical References
  • Integrin alpha4beta1
  • Animals
  • Autoimmunity (immunology)
  • B-Lymphocytes (immunology, metabolism)
  • Disease Susceptibility
  • Encephalomyelitis, Autoimmune, Experimental (immunology, metabolism)
  • Humans
  • Integrin alpha4beta1 (deficiency)
  • Leukocytes (immunology, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Th17 Cells (immunology, metabolism)

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