The story of TIM family proteins and the regulation of viral infection just gets more and more interesting. We’ve previously explored the role of TIM-1 in mediating Ebola and Marburg virus infection. We’ve now published our newest work on modulation of HIV cellular infection by TIM-1: http://www.pnas.org/content/early/2014/08/14/1404851111.abstract
Sugarcone Biotech is pleased to congratulate our collaborators Gabriela Constantin and colleagues on the publication in Immunity of the paper entitled
TIM-1 Glycoprotein Binds the Adhesion Receptor P-Selectin and Mediates T Cell Trafficking during Inflammation and Autoimmunity by Stefano Angiari, Tiziano Donnarumma, Barbara Rossi, Silvia Dusi, Enrica Pietronigro, Elena Zenaro, Vittorina Della Bianca, Lara Toffali, Gennj Piacentino, Simona Budui, Paul Rennert, Sheng Xiao, Carlo Laudanna, Jose M. Casasnovas, Vijay K. Kuchroo, and Gabriela Constantin.
published online ahead of print today, April 3 2014 DOI: http://dx.doi.org/10.1016/j.immuni.2014.03.004
The paper makes extensive use of antibodies and proteins developed by SugarCone founder Paul Rennert, and Biogen Idec colleagues. This elegant work details a previously unknown function of TIM-1 in regulating T cell movement in the inflamed vasculature, thereby controlling local inflammation. This new biology complements the role previously described for TIM-1 in mediating lung allergic responses. Alongside our recently published work in Ebola virus cellular infection, we begin to appreciate the role of TIM-1 in diverse aspects of infection, immunity, chronic inflammation and autoimmunity. See http://www.ncbi.nlm.nih.gov/pubmed/21911007 for more on this important protein.
Here is the summary of the paper from Immunity:
- •TIM-1 mediates Th1 and Th17 cell capture and rolling on P-selectin in vitro
- •TIM-1 is a major P-selectin ligand controlling T cell adhesion in inflamed vessels
- •Both mucin and IgV domains of TIM-1 are required for the interaction with P-selectin
- •TIM-1-mediated adhesion controls autoimmune and inflammatory disease development
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.