title: CD103+ Dendritic Cells Elicit CD8+ T Cell Responses to Accelerate Kidney Injury in Adriamycin Nephropathy.
abstract: CD103(+) dendritic cells (DCs) in nonlymphoid organs exhibit two main functions: maintaining tolerance by induction of regulatory T cells and protecting against tissue infection through cross-presentation of foreign antigens to CD8(+) T cells. However, the role of CD103(+) DCs in kidney disease is unknown. In this study, we show that CD103(+) DCs are one of four subpopulations of renal mononuclear phagocytes in normal kidneys. CD103(+) DCs expressed DC-specific surface markers, transcription factors, and growth factor receptors and were found in the kidney cortex but not in the medulla. The number of kidney CD103(+) DCs was significantly higher in mice with adriamycin nephropathy (AN) than in normal mice, and depletion of CD103(+) DCs attenuated kidney injury in AN mice. In vitro, kidney CD103(+) DCs preferentially primed CD8(+) T cells and did not directly induce tubular epithelial cell apoptosis. Adoptive transfer of CD8(+) T cells significantly exacerbated kidney injury in AN SCID mice, whereas depletion of CD103(+) DCs in these mice impaired activation and proliferation of transfused CD8(+) T cells and prevented the exacerbation of kidney injury associated with this transfusion. In conclusion, kidney CD103(+) DCs display a pathogenic role in murine CKD via activation of CD8(+) T cells.
authors.affiliation: Centre for Transplant and Renal Research and qi.cao@sydney.edu.au.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Emergency Department, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; and.
authors.forename: Junyu
authors.initials: J
authors.lastname: Lu
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Changqi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Flow Cytometry Facility, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia;
authors.forename: Xin Maggie
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Lee
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Chengshi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Alexander
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: David C H
authors.initials: DC
authors.lastname: Harris
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D015703:Antigens, CD / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004317:Doxorubicin / Q000009:adverse effects*; D039001:Integrin alpha Chains / Q000276:immunology*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000276:immunology*; D051379:Mice
chemical_list: D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins; D004317:Doxorubicin
keywords: CD103+ dendritic cell; CD8 T cell; adriamycin nephropathy; renal mononuclear phagocyte