Journal
CELL REPORTS
Volume 30, Issue 11, Pages 3806-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.02.062
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Funding
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI15C3134]
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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.
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