Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
FoxL1<sup>+</sup>-Telocytes (TC<sup>FoxL1+</sup>) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TC<sup>FoxL1+</sup> (<i>BmpR1...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/30890b31f2f24b6eaf282b4bf92e143a |
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| Sumario: | FoxL1<sup>+</sup>-Telocytes (TC<sup>FoxL1+</sup>) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TC<sup>FoxL1+</sup> (<i>BmpR1a</i><sup>ΔFoxL1+</sup>) initiated colonic neoplasia. Although TC<sup>FoxL1+</sup> are modulated in IBD patients, their specific role in this pathogenesis remains unclear. Thus, we investigated how the loss of BMP signalling in TC<sup>FoxL1+</sup> influences the severity of inflammation and fosters epithelial recovery after inflammatory stress. <i>BmpR1a</i> was genetically ablated in mouse colonic TC<sup>FoxL1+</sup>. Experimental colitis was performed using a DSS challenge followed by recovery steps to assess wound healing. Physical barrier properties, including mucus composition and glycosylation, were assessed by alcian blue staining, immunofluorescences and RT-qPCR. We found that <i>BmpR1a</i><sup>ΔFoxL1+</sup> mice had impaired mucus quality, and upon exposure to inflammatory challenges, they had increased susceptibility to experimental colitis and delayed healing. In addition, defective BMP signalling in TC<sup>FoxL1+</sup> altered the functionality of goblet cells, thereby affecting mucosal structure and promoting bacterial invasion. Following inflammatory stress, TC<sup>FoxL1+</sup> with impaired BMP signalling lose their homing signal for optimal distribution along the epithelium, which is critical in tissue regeneration after injury. Overall, our findings revealed key roles of BMP signalling in TC<sup>FoxL1+</sup> in IBD pathogenesis. |
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