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

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.

• Authors: 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
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 145 Issue 3 Pg. 230-40 (Dec 2012) ISSN: 1521-7035 [Electronic] United States
• PMID: 23117395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• 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

Topics

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