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Natural killer T cell/IL-4 signaling promotes bone marrow-derived fibroblast activation and M2 macrophage-to-myofibroblast transition in renal fibrosis.

Natural killer T cell/IL-4 signaling promotes bone marrow-derived fibroblast activation and M2 macrophage-to-myofibroblast transition in renal fibrosis.

Authors :
Liu B
Jiang J
Liang H
Xiao P
Lai X
Nie J
Yu W
Gao Y
Wen S
Source :
International immunopharmacology [Int Immunopharmacol] 2021 Sep; Vol. 98, pp. 107907. Date of Electronic Publication: 2021 Jul 06.
Publication Year :
2021

Abstract

Renal fibrosis is a histological manifestation of chronic kidney disease. Natural killer T (NKT) cells have a critical role in the pathogenesis of fibrotic disorder. However, the role of NKT cells in regulating kidney fibrosis remains largely unknown. In the current study, we showed that the percentages of NKT <superscript>+</superscript> cells and NKT <superscript>+</superscript> -IL-4 <superscript>+</superscript> cells were notably increased in folic acid (FA) and obstructive nephropathy. CD1d deficiency protected mice from renal fibrosis induced by FA and obstructive injury. Specifically, Loss of CD1d reduced bone marrow-derived myofibroblasts and CD206 <superscript>+</superscript> /α-smooth muscle actin <superscript>+</superscript> cells in the kidneys of injured mice. But mice treated with α-galactosylceramide (α-GC, a specific activator of NKT cells) developed more severe fibrosis, accumulated more myeloid myofibroblasts and M2 macrophages-myofibroblasts transition (M2MMT) cells in FA injured kidneys. Furthermore, IL-4 expression was markedly reduced in CD1d deficiency mice but increased in α-GC-treated mice. Administration of IL-4 abrogates the inhibiting effect of CD1d deficiency on renal fibrosis, bone marrow-derived fibroblasts activation, and M2MMT in FA injured kidneys. Conversely, pharmacological inhibition of IL-4 attenuated the development of renal fibrosis, decreased bone marrow-derived myofibroblasts, and suppressed M2MMT. Thus, this study revealed a novel role of NKT cells in the bone marrow-derived fibroblasts activation and M2MMT during renal fibrosis. Targeting NKT cell/IL-4 signaling may be an effective treatment for renal fibrosis.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1878-1705
Volume :
98
Database :
MEDLINE
Journal :
International immunopharmacology
Publication Type :
Academic Journal
Accession number :
34243040
Full Text :
https://doi.org/10.1016/j.intimp.2021.107907