C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy.
C5a
CCL2
IgA nephropathy
Vδ1 T cell
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
21
07
2023
revised:
02
10
2023
accepted:
10
10
2023
medline:
27
11
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Mucosal immune-associated γδ T cells have been implicated in IgA nephropathy (IgAN). However, the involvement of Vδ1 T cells, the major γδ T cells subtype, in renal damage and the mechanism underlying their migration from peripheral blood to kidney in IgAN remain unclear. Clinical data from IgAN patients and healthy controls (HC) were analyzed. Phenotypes and chemokine receptors of γδ T cell were compared between IgAN patients and HC. Immunohistochemistry and immunofluorescence were performed to assess the infiltration of γδ T cell subsets and the expression of chemokine in renal tissues. In vitro, C5a was used to stimulate the human glomerular mesangial cells (HMCs) and chemotaxis experiment was used to examine Vδ1 T cells migration. Correlation between Vδ1 T cells and related clinical indicators were analyzed. IgAN patients exhibited decreased Vδ1 T cell in blood but increased levels in kidneys compared to HC. Increased CCR2-expressing Vδ1 T cells and serum level of CCL2 were observed in IgAN patients. CCL2 co-localized with CCR2 in HMCs of IgAN. In vitro, C5a enhanced Vδ1 T cells recruitment by HMCs through CCL2-CCR2 axis. Importantly, circulating Vδ1 T cell levels showed a negatively correlated with both the urinary protein creatinine ratio (UACR) and 24-hour urine protein (UP). Moreover, kidney infiltration of Vδ1 cells positively correlated with UACR, UP, mesangial hyperplasia and renal tubule atrophy/interstitial fibrosis in IgAN. C5a-induced production of CCL2 by HMCs facilitates Vδ1 T cells recruitment via the CCL2-CCR2 axis, contributing to renal damage in IgAN.
Sections du résumé
BACKGROUND
BACKGROUND
Mucosal immune-associated γδ T cells have been implicated in IgA nephropathy (IgAN). However, the involvement of Vδ1 T cells, the major γδ T cells subtype, in renal damage and the mechanism underlying their migration from peripheral blood to kidney in IgAN remain unclear.
METHODS
METHODS
Clinical data from IgAN patients and healthy controls (HC) were analyzed. Phenotypes and chemokine receptors of γδ T cell were compared between IgAN patients and HC. Immunohistochemistry and immunofluorescence were performed to assess the infiltration of γδ T cell subsets and the expression of chemokine in renal tissues. In vitro, C5a was used to stimulate the human glomerular mesangial cells (HMCs) and chemotaxis experiment was used to examine Vδ1 T cells migration. Correlation between Vδ1 T cells and related clinical indicators were analyzed.
RESULTS
RESULTS
IgAN patients exhibited decreased Vδ1 T cell in blood but increased levels in kidneys compared to HC. Increased CCR2-expressing Vδ1 T cells and serum level of CCL2 were observed in IgAN patients. CCL2 co-localized with CCR2 in HMCs of IgAN. In vitro, C5a enhanced Vδ1 T cells recruitment by HMCs through CCL2-CCR2 axis. Importantly, circulating Vδ1 T cell levels showed a negatively correlated with both the urinary protein creatinine ratio (UACR) and 24-hour urine protein (UP). Moreover, kidney infiltration of Vδ1 cells positively correlated with UACR, UP, mesangial hyperplasia and renal tubule atrophy/interstitial fibrosis in IgAN.
CONCLUSIONS
CONCLUSIONS
C5a-induced production of CCL2 by HMCs facilitates Vδ1 T cells recruitment via the CCL2-CCR2 axis, contributing to renal damage in IgAN.
Identifiants
pubmed: 37862725
pii: S1567-5769(23)01391-7
doi: 10.1016/j.intimp.2023.111065
pii:
doi:
Substances chimiques
CCL2 protein, human
0
CCR2 protein, human
0
Chemokine CCL2
0
Chemokines
0
Receptors, CCR2
0
C5AR1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111065Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.