title: MAP4K4 deficiency in CD4(+) T cells aggravates lung damage induced by ozone-oxidized black carbon particles.
abstract: As the main composition of combustion, black carbon (BC) is becoming more and more noticeable at home and abroad. Ozone-oxidized black carbon (oBC) was produced through aging of ozone, one of the near-surface pollutants, to black carbon. And oBC was found to be more oxidation and cell toxicity when compared with BC. Besides, as a key cell of immunity, whether CD4(+) T cell would involve in lung inflammation induced by particular matter is still unclear. This study aims to observe the effect of oBC on lung damage in mice and discuss how the functional MAP4K4 defect CD4(+) T cells (conditional knockout of MAP4K4) presents its role in this process. In our study, MAP4K4 deletion in CD4(+) T cells (MAP4K4 cKO) could increase cell number of macrophages, lymphocytes and neutrophils in bronchoalveolar lavage fluid (BALF) exposed to oBC. MAP4K4 deletion in CD4(+) T cell also affected CD4(+) T cell differentiation in mediastinal lymph nodes after oBC stimulation. The number of CD4(+) IL17(+) T cell increased obviously. The levels of IL-6 mRNA of lung in MAP4K4 cKO mice was higher than that in wild type mice after exposed to oBC, while the level of IL-6 in BALF had the same trend. Histological examination showed that MAP4K4 deletion in CD4(+) T cells affected lung inflammation induced by oBC. Results indicated that MAP4K4 cKO in CD4(+) T cells upgraded the level of inflammation in lung when exposed to oBC, which may be connected to the CD4(+) T cell differentiation and JNK, ERK and P38 pathways.
authors: 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, Beijing, 100191, PR China.
authors: Ming
authors: M
authors: Jin
authors: 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, Beijing, 100191, PR China.
authors: Hongqian
authors: H
authors: Chu
authors: 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, Beijing, 100191, PR China.
authors: Yuan
authors: Y
authors: Li
authors: 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, Beijing, 100191, PR China.
authors: Xi
authors: X
authors: Tao
authors: 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, Beijing, 100191, PR China.
authors: Zhiyuan
authors: Z
authors: Cheng
authors: 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, Beijing, 100191, PR China.
authors: Yao
authors: Y
authors: Pan
authors: 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, Beijing, 100191, PR China.
authors: Qinghe
authors: Q
authors: Meng
authors: 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, Beijing, 100191, PR China.
authors: Leilei
authors: L
authors: Li
authors: 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, Beijing, 100191, PR China.
authors: Xiaohong
authors: X
authors: Hou
authors: State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, PR China.
authors: Yueyue
authors: Y
authors: Chen
authors: 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, Beijing, 100191, PR China.
authors: Hongpeng
authors: H
authors: Huang
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, 100191, PR China.
authors: Guang
authors: G
authors: Jia
authors: State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, PR China.
authors: Jing
authors: J
authors: Shang
authors: State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, PR China.
authors: Tong
authors: T
authors: Zhu
authors: 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, Beijing, 100191, PR China.
authors: Lanqin
authors: L
authors: Shang
authors: 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, Beijing, 100191, PR China.
authors: Weidong
authors: W
authors: Hao
authors: 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, Beijing, 100191, PR China. Electronic address: weixt1010@gmail.com.
authors: Xuetao
authors: X
authors: Wei
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002606:Charcoal / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D055370:Lung Injury / Q000139:chemically induced* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010126:Ozone / Q000737:chemistry*; D010316:Particle Size; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000393:Air Pollutants; D002606:Charcoal; D010126:Ozone; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase
keywords: CD4(+) IL17(+) T cell; CD4(+) T cell; Lung inflammation; MAP4K4; Ozone-oxidized black carbon