A stromal progenitor and ILC2 niche promotes muscle eosinophilia and fibrosis-associated gene expression
| Autor: | Therese T. Cristal, Rodolfo Rios, Gerald Coulis, Adam K. Savage, Tahseen Mozaffar, Brandon S. Hughes, Scott Q. Harper, Jenna M. Kastenschmidt, Rachel E. Ayer, Archis A. Deshpande, S. Armando Villalta, Ali H. Mannaa, Richard M. Locksley, Rayan Yahia, Philip K. Farahat, Carlee R. Giesige, Phillip Pham |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
type II innate immunity Duchenne muscular dystrophy Medical Physiology Gene Expression chemokines ILC2 Mice 0302 clinical medicine Eosinophilia Innate 2.1 Biological and endogenous factors Lymphocytes Biology (General) Muscular dystrophy Aetiology Lung Pediatric fibro/adipogenic progenitors Innate lymphoid cell Skeletal CC Intestines medicine.anatomical_structure Chemokines CC Muscle Stem Cell Research - Nonembryonic - Non-Human medicine.symptom muscular dystrophy Duchenne/ Becker Muscular Dystrophy QH301-705.5 interleukin-33 Intellectual and Developmental Disabilities (IDD) Inflammation Biology Article General Biochemistry Genetics and Molecular Biology muscle inflammation 03 medical and health sciences Rare Diseases medicine Genetics Animals Humans Muscle Skeletal Interleukin 5 Cell Proliferation Gene Expression Profiling Inbred mdx Immunity Skeletal muscle Mesenchymal Stem Cells Fibroblasts Interleukin-33 medicine.disease Duchenne ST2 Stem Cell Research Fibrosis Immunity Innate Brain Disorders Muscular Dystrophy Duchenne Interleukin 33 Eosinophils 030104 developmental biology Musculoskeletal Immunology Mice Inbred mdx Interleukin-2 interleukin-5 Biochemistry and Cell Biology Interleukin-5 030217 neurology & neurosurgery |
| Zdroj: | Cell reports, vol 35, iss 2 Cell reports Cell Reports, Vol 35, Iss 2, Pp 108997-(2021) |
| Popis: | SUMMARY Despite the well-accepted view that chronic inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), the function and regulation of eosinophils remain an unclear facet of type II innate immunity in dystrophic muscle. We report the observation that group 2 innate lymphoid cells (ILC2s) are present in skeletal muscle and are the principal regulators of muscle eosinophils during muscular dystrophy. Eosinophils were elevated in DMD patients and dystrophic mice along with interleukin (IL)-5, a major eosinophil survival factor that was predominantly expressed by muscle ILC2s. We also find that IL-33 was upregulated in dystrophic muscle and was predominantly produced by fibrogenic/adipogenic progenitors (FAPs). Exogenous IL-33 and IL-2 complex (IL-2c) expanded muscle ILC2s and eosinophils, decreased the cross-sectional area (CSA) of regenerating myofibers, and increased the expression of genes associated with muscle fibrosis. The deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia and impaired the induction of IL-5 and fibrosis-associated genes. Our findings highlight a FAP/ILC2/eosinophil axis that promotes type II innate immunity, which influences the balance between regenerative and fibrotic responses during muscular dystrophy. In brief Immune cells that comprise type II innate immunity coalesce to regulate tissue repair and fibrosis. Kastenschmidt et al. report that ILC2s reside in skeletal muscle, are activated in muscular dystrophy, and promote muscle eosinophilia. Stromal progenitors expressed IL-33, which expanded ILC2s and promoted a transcriptional program associated with muscle fibrosis. Graphical Abstract |
| Databáze: | OpenAIRE |
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