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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.
- 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.)
- Subjects :
- Animals
Antigens, CD1d genetics
Cell Communication immunology
Disease Models, Animal
Fibrosis
Folic Acid administration & dosage
Folic Acid toxicity
Humans
Kidney drug effects
Kidney immunology
Macrophages immunology
Macrophages pathology
Male
Mice
Mice, Knockout
Myofibroblasts immunology
Myofibroblasts pathology
Natural Killer T-Cells metabolism
Renal Insufficiency, Chronic chemically induced
Renal Insufficiency, Chronic genetics
Renal Insufficiency, Chronic pathology
Interleukin-4 metabolism
Kidney pathology
Natural Killer T-Cells immunology
Renal Insufficiency, Chronic immunology
Subjects
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