Dystrophic muscle is characterised by chronic injury, and a steady recruitment of inflammatory Ly6Chi monocytes. Recent studies have identified the spleen as the dominant reservoir of these cells during chronic inflammation. Here we investigated the hitherto unexplored contribution of splenic Ly6Chi monocytes to dystrophic muscle pathology. Using the mdx mouse model of muscular dystrophy, we show that Ly6Chi monocytes accumulate in great numbers in the spleen over the course of the disease. The chemokine receptor CCR2 was upregulated on Ly6Chi monocytes in mdx spleen before disease onset, thereby enabling their recruitment to dystrophic muscle. Splenectomy performed before disease onset significantly reduced the number of Ly6Chi monocytes infiltrating dystrophic limb muscle. Moreover, in the absence of splenic Ly6Chi monocytes there was a significant reduction in dystrophic muscle inflammation and necrosis, along with improved regeneration during early disease. However, during late disease, lack of splenic Ly6Chi monocytes adversely affected muscle fiber repair, due to a delay in the phenotypic shift of pro-inflammatory F4/80+/Ly6Chi/CD206lo to anti-inflammatory F4/80+/Ly6Clo/CD206+ macrophages. Overall, we show that the spleen is an indispensable source of Ly6Chi monocytes in muscular dystrophy, and that splenic monocytes are critical players in both muscle fiber injury and repair.

Splenic Ly6Chi monocytes are critical players in dystrophic muscle injury and repair / Rizzo, Giuseppe; Di Maggio, Rosanna; Benedetti, Anna; Morroni, Jacopo; Bouche, Marina; Lozanoska-Ochser, Biliana. - In: JCI INSIGHT. - ISSN 2379-3708. - 5:2(2020), pp. 1-13. [10.1172/jci.insight.130807]

Splenic Ly6Chi monocytes are critical players in dystrophic muscle injury and repair

Di Maggio, Rosanna
Secondo
;
Benedetti, Anna;Morroni, Jacopo;Bouche, Marina
Penultimo
;
Lozanoska-Ochser, Biliana
Ultimo
2020

Abstract

Dystrophic muscle is characterised by chronic injury, and a steady recruitment of inflammatory Ly6Chi monocytes. Recent studies have identified the spleen as the dominant reservoir of these cells during chronic inflammation. Here we investigated the hitherto unexplored contribution of splenic Ly6Chi monocytes to dystrophic muscle pathology. Using the mdx mouse model of muscular dystrophy, we show that Ly6Chi monocytes accumulate in great numbers in the spleen over the course of the disease. The chemokine receptor CCR2 was upregulated on Ly6Chi monocytes in mdx spleen before disease onset, thereby enabling their recruitment to dystrophic muscle. Splenectomy performed before disease onset significantly reduced the number of Ly6Chi monocytes infiltrating dystrophic limb muscle. Moreover, in the absence of splenic Ly6Chi monocytes there was a significant reduction in dystrophic muscle inflammation and necrosis, along with improved regeneration during early disease. However, during late disease, lack of splenic Ly6Chi monocytes adversely affected muscle fiber repair, due to a delay in the phenotypic shift of pro-inflammatory F4/80+/Ly6Chi/CD206lo to anti-inflammatory F4/80+/Ly6Clo/CD206+ macrophages. Overall, we show that the spleen is an indispensable source of Ly6Chi monocytes in muscular dystrophy, and that splenic monocytes are critical players in both muscle fiber injury and repair.
2020
inflammation; monocytes; muscle; muscle biology; neuromuscular disease
01 Pubblicazione su rivista::01a Articolo in rivista
Splenic Ly6Chi monocytes are critical players in dystrophic muscle injury and repair / Rizzo, Giuseppe; Di Maggio, Rosanna; Benedetti, Anna; Morroni, Jacopo; Bouche, Marina; Lozanoska-Ochser, Biliana. - In: JCI INSIGHT. - ISSN 2379-3708. - 5:2(2020), pp. 1-13. [10.1172/jci.insight.130807]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1348219
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