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

Daniel C. Bullard, Xianzhen Hu, David Crawford, Kristin Mcdonald, Theresa N. Ramos, Scott R. Barnum

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1194-1199
Number of pages6
JournalEuropean Journal of Immunology
Volume44
Issue number4
DOIs
StatePublished - Apr 2014
Externally publishedYes

Keywords

  • Adhesion molecules
  • Alternative splicing
  • Central nervous system
  • Demyelinating disease
  • Transgenic animals

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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