title: Losartan and Dexamethasone may inhibit chemotaxis to reduce the infiltration of Th22 cells in IgA nephropathy.
abstract: Angiotensin II is considered a major profibrotic factor that is involved in tissue remodeling processes, as the inhibition of Angiotensin II can halt renal inflammatory processes. Dexamethasone, an important anti-inflammatory and immunosuppressive agent, has been widely used to treat renal disease for decades. In this study, we explored the frequency of Th22 cells in a mouse model of IgA nephropathy and compared the possible effects of Losartan and Dexamethasone on Th22 cells. The experiments were performed using 6-week-old BALB/c female mice in an established IgA nephropathy model. The mice were randomly separated into 4 groups, which were administered Losartan (30mg/kg/d) or Dexamethasone (10mg/kg/d) and subjected to IgA nephropathy or the normal control treatment for 1month. The frequency of Th22 cells was measured via flow cytometry, and the relative pathological changes in renal morphology were measured with different pathological staining methods. Immunohistochemistry was performed to verify the expression of CCR10 and CCL27, which is specialized receptor on Th22 cells and its corresponding chemokine, respectively. The concentrations of CCL27 and IL-22 in renal tissue homogenates and sera were detected using ELISAs. Losartan and Dexamethasone differentially decreased the frequency of Th22 cells after 1month, and mesangial cell proliferation was also improved. Moreover, the expression of CCR10, CCL27 and IL-22 was reduced by treatment with either drug. However, significant differences between Losartan and Dexamethasone were not observed. Based on these findings, Losartan and Dexamethasone may suppress inflammatory responses by inhibiting the chemotaxis of Th22 cells in IgA nephropathy.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Chenggen
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Meng
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. Electronic address: xiaoping.x@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054425:Chemokine CCL27 / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007378:Interleukins / Q000378:metabolism*; D019808:Losartan / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D054447:Receptors, CCR10 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D054425:Chemokine CCL27; D003907:Dexamethasone; D007166:Immunosuppressive Agents; D007378:Interleukins; D019808:Losartan; D054447:Receptors, CCR10; D000097043:Interleukin-22; C515707:Ccr10 protein, mouse
keywords: CCL27; CCR10; Dexamethasone; IgA nephropathy; Losartan; Th22 cells