Exacerbation of spontaneous autoimmune nephritis following regulatory T cell depletion in B cell lymphoma 2-interacting mediator knock-out mice.
Regulatory T cells (Tregs) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of Tregsor their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of Tregsin the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of Tregsin a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting Tregs. Bim is a pro-apoptotic member of the B cell lymphoma 2 (Bcl-2) family. Bim knock-out (Bim-/-) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that Tregdepletion in Bim-/-mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild-type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17α, interferon (IFN)-γ and tumour necrosis factor (TNF)-α were increased significantly after Tregdepletion in Bim-/-mice. This study demonstrates that transient depletion of Tregsleads to enhanced self-reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim-deficient mice.
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
Y M
YM
Wang
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
G Y
GY
Zhang
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
Y
Y
Wang
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
M
M
Hu
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
J J
JJ
Zhou
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
A
A
Sawyer
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
Q
Q
Cao
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
Y
Y
Wang
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
G
G
Zheng
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
V W S
VW
Lee
Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia.
D C H
DC
Harris
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
S I
SI
Alexander
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D000072224:Bcl-2-Like Protein 11 / Q000172:deficiency / Q000235:genetics*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D011507:Proteinuria; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10
B cell lymphoma (Bcl) 2; Bim knock-out mice; regulatory T cells; spontaneous autoimmune glomerulonephritis