title: MAP4K4 deletion inhibits proliferation and activation of CD4(+) T cell and promotes T regulatory cell generation in vitro.
abstract: CD4(+) T cells are critical for adaptive immunity. MAP4K4 is a key member of germinal center kinase group. However, the physiological function of MAP4K4 in primary CD4(+) T cells is still unclear. In this study, it was demonstrated that in vitro, MAP4K4 deletion remarkably suppressed CD4(+) T cell proliferation in response to phorbol 12-myristate 13-acetate (PMA) and ionomycin, which was not due to enhancing cell apoptosis. Additionally, MAP4K4 was required for the activation of CD4(+) T cells. MAP4K4 deletion significantly down-regulated expression of interleukin 2 (IL-2) and interferon-γ (IFN-γ), while notably up-regulating the expression of regulatory T cells (Treg) transcription factor Foxp3 in peripheral CD4(+) T cells. Furthermore, western blot analysis indicated that CD4(+) T cells lacking MAP4K4 failed to phosphorylate Jnk, Erk, p38 and PKC-θ. Thus, our results provide the evidence that MAP4K4 is essential for CD4(+) T cell proliferation, activation and cytokine production.
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Hongpeng
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Qiuqiong
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Roche R&D Center (China) Ltd., Shanghai 201203, PR China.
authors.forename: Haizhou
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, PR China. Electronic address: whao@bjmu.edu.cn.
authors.forename: Weidong
authors.initials: W
authors.lastname: Hao
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, PR China. Electronic address: weixt@263.net.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Wei
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D017353:Gene Deletion; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015759:Ionomycin; D007527:Isoenzymes / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D007376:Interleukin-2; D015759:Ionomycin; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D017346:Protein Serine-Threonine Kinases; D013755:Tetradecanoylphorbol Acetate; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase; C498833:Foxp3 protein, mouse; C489593:Prkcq protein, mouse
keywords: CD4(+) T cells; MAP4K4; PKC-θ; Treg