Regulatory T Cells Accelerate the Repair Process of Renal Fibrosis by Regulating Mononuclear Macrophages.
Macrophages
Mouse model
Obstructive nephropathy
Regulatory T cells
Renal fibrosis
Journal
The American journal of the medical sciences
ISSN: 1538-2990
Titre abrégé: Am J Med Sci
Pays: United States
ID NLM: 0370506
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
11
02
2020
revised:
18
11
2020
accepted:
29
01
2021
pubmed:
6
3
2021
medline:
21
7
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
We aimed to investigate the mechanisms of renal fibrosis and explore the effect of CD4+CD25+Foxp3+ regulatory T cells (Treg) on renal fibrosis after the obstruction was removed. Fifty-five C57BL/6 mice were randomly divided into three groups: the unilateral ureteral obstruction (UUO) group, the relief for unilateral ureteral obstruction (RUUO) group, and the RUUO+Treg group. Renal fibrosis indexes of RUUO mice were evaluated using hematoxylin and eosin (HE) and, Masson staining and immunohistochemistry after CD4+CD25+Treg cells were injected into the tail vein at the moment of recanalization. We detected the levels of Treg, M1, and M2 markers by flow cytometry, and the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, IL-6 and IL-10 using ELISA. The tubular necrosis score, AO value of α-SMA (smooth muscle actin), and collagen area on the 3rd and 14th days post RUUO were up-regulated compared with the 7th day post RUUO (P<0.05). After injection of Treg via tail vein, the tubular necrosis score, AO value of α-SMA, TGF-β1 level, and collagen area in the RUUO+Treg group on the 14th day were down-regulated compared with the RUUO group (P<0.05). Moreover, Treg could transform M1 macrophages into M2 macrophages, manifesting as up-regulated expression of CD206 compared with the RUUO group (P<0.05). Treg could also down-regulate the secretion of IL-6 and IL-1β while up-regulating the secretion of IL-10 in vitro compared with the M1 group (P<0.05). The kidney could deteriorate into a state of injury and fibrosis after the obstruction was removed, and Treg could effectively protect the kidney function.
Sections du résumé
BACKGROUND
We aimed to investigate the mechanisms of renal fibrosis and explore the effect of CD4+CD25+Foxp3+ regulatory T cells (Treg) on renal fibrosis after the obstruction was removed.
METHODS
Fifty-five C57BL/6 mice were randomly divided into three groups: the unilateral ureteral obstruction (UUO) group, the relief for unilateral ureteral obstruction (RUUO) group, and the RUUO+Treg group. Renal fibrosis indexes of RUUO mice were evaluated using hematoxylin and eosin (HE) and, Masson staining and immunohistochemistry after CD4+CD25+Treg cells were injected into the tail vein at the moment of recanalization. We detected the levels of Treg, M1, and M2 markers by flow cytometry, and the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, IL-6 and IL-10 using ELISA.
RESULTS
The tubular necrosis score, AO value of α-SMA (smooth muscle actin), and collagen area on the 3rd and 14th days post RUUO were up-regulated compared with the 7th day post RUUO (P<0.05). After injection of Treg via tail vein, the tubular necrosis score, AO value of α-SMA, TGF-β1 level, and collagen area in the RUUO+Treg group on the 14th day were down-regulated compared with the RUUO group (P<0.05). Moreover, Treg could transform M1 macrophages into M2 macrophages, manifesting as up-regulated expression of CD206 compared with the RUUO group (P<0.05). Treg could also down-regulate the secretion of IL-6 and IL-1β while up-regulating the secretion of IL-10 in vitro compared with the M1 group (P<0.05).
CONCLUSIONS
The kidney could deteriorate into a state of injury and fibrosis after the obstruction was removed, and Treg could effectively protect the kidney function.
Identifiants
pubmed: 33667434
pii: S0002-9629(21)00045-8
doi: 10.1016/j.amjms.2021.01.022
pii:
doi:
Substances chimiques
Inflammation Mediators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
776-785Informations de copyright
Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflict of interest.