Expression of a single ICAM-1 isoform on T cells is sufficient for development of experimental autoimmune encephalomyelitis

Academic Article

Abstract

  • Intercellular adhesion molecule-1 (ICAM-1) plays an important role in leukocyte trafficking, induction of cellular immune responses, and immunological synapse formation. As a member of the immunoglobulin superfamily of adhesion proteins, ICAM-1 is composed of repeating Ig-like domains, a transmembrane domain, and short cytoplasmic tail that participates in intracellular signaling events. At least seven ICAM-1 protein isoforms are generated by alternative splicing, however little is known regarding their immunobiology. We have previously shown using different lines of ICAM-1 mutant mice (Icam1tm1Jcgr and Icam1tm1Bay) that expression of alternatively spliced ICAM-1 isoforms can significantly influence the disease course during the development of EAE. In this study, we show using a newly developed transgenic mouse (CD2-Icam1D4del/Icam1null) that T-cell-specific expression of a single ICAM-1 isoform composed of Ig domains 1, 2, 3, and 5 can mediate the initiation and progression of EAE. Our results indicate that the ICAM-1 isoform lacking Ig domain 4 can drive pathogenesis in demyelinating disease and may be a novel therapeutic target for treating multiple sclerosis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 18939598
  • Author List

  • Bullard DC; Hu X; Crawford D; Mcdonald K; Ramos TN; Barnum SR
  • Start Page

  • 1194
  • End Page

  • 1199
  • Volume

  • 44
  • Issue

  • 4