A Role for the Neuronal Protein Collapsin Response Mediator Protein 2 in T Lymphocyte Polarization and Migration

• Published in: Journal of Immunology Vol. 175; no. 11; pp. 7650 - 7660
• Main Authors: Vincent, Peggy, Collette, Yves, Marignier, Romain, Vuaillat, Carine, Rogemond, Veronique, Davoust, Nathalie, Malcus, Christophe, Cavagna, Sylvie, Gessain, Antoine, Machuca-Gayet, Irma, Belin, Marie-Francoise, Quach, Tam, Giraudon, Pascale
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-12-2005
• Subjects: Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - metabolism; Blotting, Western; Cell Movement - immunology; Flow Cytometry; Gene Silencing; HLA-DR Antigens - immunology; HLA-DR Antigens - metabolism; HTLV-I Infections - immunology; Humans; Intercellular Signaling Peptides and Proteins; Jurkat Cells; Lectins, C-Type; Nerve Tissue Proteins; Proteins - immunology; Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - virology; Transfection
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.175.11.7650

The semaphorin-signaling transducer collapsin response mediator protein 2 (CRMP2) has been identified in the nervous system where it mediates Sema3A-induced growth cone navigation. In the present study, we provide first evidence that CRMP2 is present in the immune system and plays a critical role in T lymphocyte function. CRMP2 redistribution at the uropod in polarized T cells, a structural support of lymphocyte motility, suggests that it may regulate T cell migration. This was evidenced in primary T cells by small-interfering RNA-mediated CRMP2 gene silencing and blocking Ab, as well as CRMP2 overexpression in Jurkat T cells tested in a chemokine- and semaphorin-mediated transmigration assay. Expression analysis in PBMC from healthy donors showed that CRMP2 is enhanced in cell subsets bearing the activation markers CD69+ and HLA-DR+. Heightened expression in T lymphocytes of patients suffering from neuroinflammatory disease with enhanced T cell-transmigrating activity points to a role for CRMP2 in pathogenesis. The elucidation of the signals and mechanisms that control this pathway will lead to a better understanding of T cell trafficking in physiological and pathological situations.