Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T cell function in ulcerative colitis

Fengmin Shi; Xiaoqin Guo; Xingwei Jiang; Ping Zhou; Yan Xiao; Tingting Zhou; Guojiang Chen; Zhi Zhao; He Xiao; Chunmei Hou; Xinying Li; Xiaomei Yang; Renxi Wang; Jiannan Feng; Beifen Shen; Yan Li; Gencheng Han

doi:10.1016/j.clim.2012.09.001

Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T cell function in ulcerative colitis

Clin Immunol. 2012 Dec;145(3):230-40. doi: 10.1016/j.clim.2012.09.001. Epub 2012 Sep 18.

Authors

Fengmin Shi¹, Xiaoqin Guo, Xingwei Jiang, Ping Zhou, Yan Xiao, Tingting Zhou, Guojiang Chen, Zhi Zhao, He Xiao, Chunmei Hou, Xinying Li, Xiaomei Yang, Renxi Wang, Jiannan Feng, Beifen Shen, Yan Li, Gencheng Han

Affiliation

¹ Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.

PMID: 23117395
DOI: 10.1016/j.clim.2012.09.001

Abstract

The pathogenesis of ulcerative colitis (UC) remains largely unclear. Here we found that T-cell Ig mucin-3 (Tim-3) and its ligand, galectin 9 (Gal-9), were significantly decreased in UC patients and in mice with dextran sodium sulfate (DSS)-induced colitis compared to controls. In addition to an enhanced Th17 response and attenuated regulatory T (Treg) cell response, there was also a significantly decreased Th1 response in UC. Levels of the Th1 cell chemokines CXCL9 and CXCL10 were significantly decreased in UC mice, partially explaining the decreased Th1 cell function in UC. Finally, administration of a putative antagonistic anti-Tim-3 antibody or of recombinant Gal-9 significantly exacerbated or attenuated DSS-induced colitis by altering the balance between different Th cell subsets. Our data suggest that a dysregulated Tim-3/Gal-9 pathway may contribute to the pathogenesis of UC. A better understanding of this pathway may shed new light on the pathogenesis of this disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal
Base Sequence
Cell Line
Chemokine CXCL10 / genetics
Chemokine CXCL9 / genetics
Colitis, Ulcerative / etiology*
Colitis, Ulcerative / immunology
Colitis, Ulcerative / metabolism
Disease Models, Animal
Galectins / metabolism
Gene Expression
Hepatitis A Virus Cellular Receptor 2
Humans
Interleukin-17 / pharmacology
Ligands
Male
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Metabolic Networks and Pathways
Mice
Mice, Inbred C57BL
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Virus / antagonists & inhibitors
Receptors, Virus / genetics
Receptors, Virus / metabolism*
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Helper-Inducer / metabolism*

Substances

Antibodies, Monoclonal
CXCL10 protein, human
CXCL9 protein, human
Chemokine CXCL10
Chemokine CXCL9
Cxcl10 protein, mouse
Cxcl9 protein, mouse
Galectins
HAVCR2 protein, human
Havcr2 protein, mouse
Hepatitis A Virus Cellular Receptor 2
Interleukin-17
LGALS9 protein, human
Ligands
Membrane Proteins
RNA, Messenger
Receptors, Virus
galectin 9, mouse