title: Oncoprotein mdig contributes to silica-induced pulmonary fibrosis by altering balance between Th17 and Treg T cells.
abstract: Mineral dust-induced gene (mdig, also named Mina53) was first identified from alveolar macrophages of the coal miners with chronic lung inflammation or fibrosis, but how this gene is involved in lung diseases is poorly understood. Here we show that heterozygotic knockout of mdig (mdig+/-) ameliorates silica-induced lung fibrosis by altering the balance between Th17 cells and Treg cells. Relative to the wild type (WT) mice, infiltration of the macrophages and Th17 cells was reduced in lungs from silica-exposed mdig+/- mice. In contrast, an increased infiltration of the T regulatory (Treg) cells to the lung intestitium was observed in the mdig+/- mice treated with silica. Both the number of Th17 cells in the lung lymph nodes and the level of IL-17 in the bronchoalveolar lavage fluids were decreased in the mdig+/- mice in response to silica. Thus, these results suggest that mdig may contribute to silica-induced lung fibrosis by altering the balance between Th17 and Treg cells. Genetic deficiency of mdig impairs Th17 cell infiltration and function, but favors infiltration of the Treg cells, the immune suppressive T cells that are able to limit the inflammatory responses by repressing the Th17 cells and macrophages.
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, USA.
authors: Chitra
authors: C
authors: Thakur
authors: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, USA.
authors: Michael
authors: M
authors: Wolfarth
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, USA.|Respiratory Medicine, The 4th Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, China.
authors: Jiaying
authors: J
authors: Sun
authors: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, USA.|Central Laboratory, The Central Hospital of Wuhan, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China.
authors: Yadong
authors: Y
authors: Zhang
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, USA.
authors: Yongju
authors: Y
authors: Lu
authors: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, USA.
authors: Lori
authors: L
authors: Battelli
authors: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, USA.
authors: Dale W
authors: DW
authors: Porter
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, USA.|Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, USA.
authors: Fei
authors: F
authors: Chen
mesh_terms: D000818:Animals; D026502:LDL-Receptor Related Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000276:immunology*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012822:Silicon Dioxide / Q000276:immunology / Q000633:toxicity*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D026502:LDL-Receptor Related Proteins; C116415:Lrp4 protein, mouse; D011973:Receptors, LDL; D012822:Silicon Dioxide