title: Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice.
abstract: Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation.
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 305-764, Republic of Korea.
authors.forename: Hyuk Soo
authors.initials: HS
authors.lastname: Eun
authors.affiliation: Laboratory of Liver Research, Biomedical Science and Engineering Interdisciplinary program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Laboratory of Liver Research, Biomedical Science and Engineering Interdisciplinary program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: Laboratory of Liver Research, Biomedical Science and Engineering Interdisciplinary program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Wonhyo
authors.initials: W
authors.lastname: Seo
authors.affiliation: Department of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Byun
authors.affiliation: Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 305-764, Republic of Korea.|Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Hyon-Seung
authors.initials: HS
authors.lastname: Yi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D006098:Granulocytes / Q000276:immunology*; D016130:Immunophenotyping; D008099:Liver / Q000473:pathology*; D018345:Mice, Knockout; D008820:Mice, Obese; D009000:Monocytes / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines