title: Expression of a single ICAM-1 isoform on T cells is sufficient for development of experimental autoimmune encephalomyelitis.
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 (Icam1(tm1Jcgr) and Icam1(tm1Bay) ) 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-Icam1(D4del) /Icam1(null) ) 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.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Hu
authors.forename: David
authors.initials: D
authors.lastname: Crawford
authors.forename: Kristin
authors.initials: K
authors.lastname: McDonald
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Ramos
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D019264:Adoptive Transfer; D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
chemical_list: D020033:Protein Isoforms; D018799:Intercellular Adhesion Molecule-1
keywords: Adhesion molecules; Alternative splicing; Central nervous system; Demyelinating disease; Transgenic animals