A role for the neuronal protein collapsin response mediator protein 2 in T lymphocyte polarization and migration.
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.
Vincent
Peggy
P
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 433 and Institut Fédératif de Recherche 19, Faculté de Médecine R. Laënnec, Lyon, France.
Collette
Yves
Y
Marignier
Romain
R
Vuaillat
Carine
C
Rogemond
Véronique
V
Davoust
Nathalie
N
Malcus
Christophe
C
Cavagna
Sylvie
S
Gessain
Antoine
A
Machuca-Gayet
Irma
I
Belin
Marie-Françoise
MF
Quach
Tam
T
Giraudon
Pascale
P
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000276:immunology*; D005434:Flow Cytometry; D020868:Gene Silencing; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D015490:HTLV-I Infections / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014162:Transfection; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006684:HLA-DR Antigens; D036341:Intercellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099192:CD69 Antigens; C095114:collapsin response mediator protein-2