title: 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.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Shi
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Guo
authors.forename: Xingwei
authors.initials: X
authors.lastname: Jiang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhao
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics; D054370:Chemokine CXCL9 / Q000235:genetics; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D037161:Galectins / Q000378:metabolism; D015870:Gene Expression; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D037161:Galectins; C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D020381:Interleukin-17; C105032:LGALS9 protein, human; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; C508186:galectin 9, mouse