2. Academic Validation
  3. TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity

TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity

  • Immunity. 2014 Apr 17;40(4):542-53. doi: 10.1016/j.immuni.2014.03.004.
Stefano Angiari 1,  Tiziano Donnarumma 1,  Barbara Rossi 1,  Silvia Dusi 1,  Enrica Pietronigro 1,  Elena Zenaro 1,  Vittorina Della Bianca 1,  Lara Toffali 2,  Gennj Piacentino 1,  Simona Budui 1,  Paul Rennert 3,  Sheng Xiao 4,  Carlo Laudanna 2,  Jose M Casasnovas 5,  Vijay K Kuchroo 4,  Gabriela Constantin 6
Affiliations

Affiliations

  • 1 Department of Pathology and Diagnostics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy.
  • 2 Department of Pathology and Diagnostics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy; The Center for Biomedical Computing (CBMC), University of Verona, Strada le Grazie 8, 37134 Verona, Italy.
  • 3 Department of Molecular Discovery and Immunobiology, Biogen Idec Inc., 12 Cambridge Center, Cambridge, MA 02146, USA.
  • 4 Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, HIM 785, Boston, MA 02115-5817, USA.
  • 5 Centro Nacional de Biotecnología, CNB-CSIC, Campus UAM, C/ Darwin, 3, Campus of Cantoblanco, E-28049 Madrid, Spain.
  • 6 Department of Pathology and Diagnostics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: [email protected].
PMID: 24703780 DOI: 10.1016/j.immuni.2014.03.004
Abstract

Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and Mucin domain 1 (TIM-1) is a P-Selectin ligand. We have shown that human and murine TIM-1 binds to P-Selectin, and that TIM-1 mediates tethering and rolling of T helper 1 (Th1) and Th17, but not Th2 and regulatory T cells on P-Selectin. Th1 and Th17 cells lacking the TIM-1 Mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but it reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 immunoglobulin variable domain was also required for P-Selectin binding. Our data demonstrate that TIM-1 is a major P-Selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease.

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