TIM-1 Glycoprotein Binds the Adhesion Receptor P-Selectin and Mediates T Cell Trafficking during Inflammation and Autoimmunity

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• 作者：Stefano Angiari¹ ; Tiziano Donnarumma¹ ; Barbara Rossi¹ ; Silvia Dusi¹ ; Enrica Pietronigro¹ ; Elena Zenaro¹ ; Vittorina Della Bianca¹ ; Lara Toffali¹ ; ⁴ ; Gennj Piacentino¹ ; Simona Budui¹ ; Paul Rennert² ; ⁶ ; Sheng Xiao³ ; Carlo Laudanna¹ ; ⁴ ; Jose M. Casasnovas⁵ ; Vijay K. Kuchroo³ ; Gabriela Constantin¹ ; ^{gabriela.constantin@univr.it" class="auth_mail}
• 刊名：Immunity
• 出版年：17 April, 2014
• 年：2014
• 卷：40
• 期：4
• 页码：542-553
• 全文大小：2790 K

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Summary

Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T聽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聽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聽cell homing, but it reduced T聽cell recruitment in a skin hypersensitivity聽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聽cell trafficking during inflammatory responses and the induction of autoimmune disease.