Regulatory T cells effectively downregulate the autoimmune anti-MPO response and ameliorate anti-MPO induced glomerulonephritis in mice.

Autor: Hu P; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Xiao H; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Elmore S; UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Agosto-Burgos C; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Hu Y; UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Hogan SL; UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ciavatta DJ; UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Falk RJ; UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Jennette JC; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Free ME; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: meghan_free@med.unc.edu.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2024 Jul; Vol. 147, pp. 103266. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1016/j.jaut.2024.103266
Abstrakt: Regulation of autoreactive cells is key for both prevention and amelioration of autoimmune disease. A better understanding of the key cell population(s) responsible for downregulation of autoreactive cells would provide necessary foundational insight for cellular-based therapies in autoimmune disease. Utilizing a mouse model of anti-myeloperoxidase (MPO) glomerulonephritis, we sought to understand which immune cells contribute to downregulation of the anti-MPO autoimmune response. MPO-/- mice were immunized with whole MPO to induce an anti-MPO response. Anti-MPO splenocytes were then transferred into recipient mice (Rag2-/- mice or WT mice). Anti-MPO titers were followed over time. After anti-MPO splenocyte transfer, WT mice are able to downregulate the anti-MPO response while anti-MPO titers persist in Rag2-/- recipients. Reconstitution with WT splenocytes into Rag2-/- recipients prior to anti-MPO splenocyte transfer enabled mice to downregulate the anti-MPO immune response. Therefore, wildtype splenocytes contain a cellular population that is capable of downregulating the autoimmune response. Through splenocyte transfer, antibody depletion experiments, and purified cell population transfers, we confirmed that the regulatory T cell (Treg) population is responsible for the downregulation of the anti-MPO autoimmune response. Further investigation revealed that functional Tregs from WT mice are capable of downregulating anti-MPO antibody production and ameliorate anti-MPO induced glomerulonephritis. These data underscore the importance of functional Tregs for control of autoimmune responses and prevention of end-organ damage due to autoimmunity.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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