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Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches.
- Source :
-
Experimental & molecular medicine [Exp Mol Med] 2024 May; Vol. 56 (5), pp. 1178-1192. Date of Electronic Publication: 2024 May 01. - Publication Year :
- 2024
-
Abstract
- Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KIT <superscript>W-SH/W-SH</superscript> ) mice to construct a model of Modic changes and found that the severity of Modic changes in KIT <superscript>W-SH/W-SH</superscript> mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Humans
Male
Mice
Middle Aged
Disease Models, Animal
Intervertebral Disc Degeneration pathology
Intervertebral Disc Degeneration metabolism
Intervertebral Disc Degeneration immunology
Intervertebral Disc Degeneration genetics
Signal Transduction
Mast Cells immunology
Mast Cells metabolism
Mice, Knockout
Subjects
Details
- Language :
- English
- ISSN :
- 2092-6413
- Volume :
- 56
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Experimental & molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38689089
- Full Text :
- https://doi.org/10.1038/s12276-024-01230-1