title: Interaction of TIM4 and TIM3 induces T helper 1 cell apoptosis.
abstract: The T helper 1 (Th1) polarization plays a critical role in the pathogenesis of a number of inflammatory disorders in the body; the remedies in the correction of polarized Th1 cells are limited. This study aims to investigate the role of T cell immunoglobulin mucin domain molecule 4 (TIM4) in the induction of Th1 cell apoptosis. In this study, polarized Th1 cells were generated from naive Th1 cells from the mouse spleen. Recombinant TIM4 was added to the culture to stimulate the polarized Th1 cells. The apoptosis of Th1 cells was assessed by flow cytometry. The expression of FasL was analyzed by chromatin immunoprecipitation, real time RT-PCR, and Western blotting. The results showed that the polarized Th1 cells expressed high levels of TIM3. After exposure of the polarized Th1 cells to TIM4 in the culture, a complex of TIM3 and TIM4 was detected on the surface of Th1 cells, which induced the Th1 cell apoptosis. The engagement of TIM3 by TIM4 increased p300 phosphorylation in Th1 cells, which further increased the levels of Fas ligand in the cells and induced Th1 cell apoptosis. In conclusion, TIM4 binds TIM3 on the surface of polarized Th1 cells to induce Th1 cell apoptosis, which may contribute to the development of Th2-dominant immune disorders.
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 4A6, Canada.
authors.forename: Rong-Ti
authors.initials: RT
authors.lastname: Ge
authors.affiliation: Shenzhen Key Laboratory of Allergy and Immunology, The Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Shenzhen Key Laboratory of Allergy and Immunology, The Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Mo
authors.affiliation: Shenzhen Key Laboratory of Allergy and Immunology, The Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Xu
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 4A6, Canada.
authors.forename: Huan-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory of Allergy and Immunology, The Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
authors.forename: Hai-Qiong
authors.initials: HQ
authors.lastname: Yu
authors.affiliation: Department of Respirology, The First Affiliated Hospital, Shenzhen University, Shenzhen, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory of Allergy and Immunology, The Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China. lzg@szu.edu.cn.|Shenzhen University, Room 722 of Medical School, 3688 Nanhai Blvd., Shenzhen, 518060, China. lzg@szu.edu.cn.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Zhan-Ju
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory of Allergy and Immunology, The Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China. pcy2356@163.com.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 4A6, Canada. pcy2356@163.com.|Shenzhen University, Room 722 of Medical School, 3688 Nanhai Blvd., Shenzhen, 518060, China. pcy2356@163.com.
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C512411:TIMD4 protein, human; D050881:E1A-Associated p300 Protein
keywords: Apoptosis; FasL; T helper 1 cell; TIM3; TIM4