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Mesenchymal Stem and Stromal Cells Harness Macrophage-Derived Amphiregulin to Maintain Tissue Homeostasis
Cited 72 time in
Web of Science
Cited 74 time in Scopus
- Authors
- Issue Date
- 2020-03
- Publisher
- Cell Press
- Citation
- Cell Reports, Vol.30 No.11, pp.3806-3820.e6
- Abstract
- The cross-talk between mesenchymal stem and stromal cells (MSCs) and macrophages is critical for the restoration of tissue homeostasis after injury. Here, we demonstrate a pathway through which MSCs instruct macrophages to resolve inflammation and preserve tissue-specific stem cells, leading to homeostasis in mice with autoimmune uveoretinitis and sterile-injury-induced corneal epithelial stem cell deficiency. Distinct from their conventional role in macro-phage reprogramming to anti-inflammatory phenotype by a PGE2-dependent mechanism, MSCs enhance the phagocytic activity of macrophages, which partly depends on the uptake of MSC mitochondria-containing extracellular vesicles. The MSC-primed macrophages increase the secretion of amphiregulin (AREG) in a phagocytosis-dependent manner. AREG is essential for MSC-primed macrophages to suppress immune responses through regulatory T (Treg) cells and to protect corneal epithelial stem cells via apoptosis inhibition and proliferation promotion. Hence, the data reveal that MSCs harness macrophage-derived AREG to maintain tissue homeostasis after injury and provide a therapeutic target in immune-mediated disease and regenerative medicine.
- ISSN
- 2211-1247
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