Macrophages are characterized by a high plasticity in response to changes in tissue microenvironment, which allows them to acquire different phenotypes and to exert essential functions in complex processes, such as tissue regeneration. Here, we report that the membrane protein Cripto plays a key role in shaping macrophage plasticity in skeletal muscle during regeneration and disease. Conditional deletion of Cripto in the myeloid lineage (CriptoMy-LOF) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, CriptoMy-LOF macrophages infiltrate the muscle, but fail to properly expand as anti-inflammatory CD206+ macrophages, which is due, at least in part, to aberrant activation of TGFβ/Smad signaling. This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206+ anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells.

Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle / Iavarone, Francescopaolo; Guardiola, Ombretta; Scagliola, Alessandra; Andolfi, Gennaro; Esposito, Federica; Serrano, Antonio; Perdiguero, Eusebio; Brunelli, Silvia; Muñoz-Cánoves, Pura; Minchiotti, Gabriella. - In: EMBO REPORTS. - ISSN 1469-221X. - 21:4(2020), pp. 1-17. [10.15252/embr.201949075]

Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle

Federica Esposito;
2020

Abstract

Macrophages are characterized by a high plasticity in response to changes in tissue microenvironment, which allows them to acquire different phenotypes and to exert essential functions in complex processes, such as tissue regeneration. Here, we report that the membrane protein Cripto plays a key role in shaping macrophage plasticity in skeletal muscle during regeneration and disease. Conditional deletion of Cripto in the myeloid lineage (CriptoMy-LOF) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, CriptoMy-LOF macrophages infiltrate the muscle, but fail to properly expand as anti-inflammatory CD206+ macrophages, which is due, at least in part, to aberrant activation of TGFβ/Smad signaling. This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206+ anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells.
2020
cripto; inflammation; macrophages; muscles; regeneration
01 Pubblicazione su rivista::01a Articolo in rivista
Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle / Iavarone, Francescopaolo; Guardiola, Ombretta; Scagliola, Alessandra; Andolfi, Gennaro; Esposito, Federica; Serrano, Antonio; Perdiguero, Eusebio; Brunelli, Silvia; Muñoz-Cánoves, Pura; Minchiotti, Gabriella. - In: EMBO REPORTS. - ISSN 1469-221X. - 21:4(2020), pp. 1-17. [10.15252/embr.201949075]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1556114
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