PMID- 32187551
OWN - NLM
STAT- MEDLINE
DCOM- 20210323
LR  - 20210323
IS  - 2211-1247 (Electronic)
VI  - 30
IP  - 11
DP  - 2020 Mar 17
TI  - Mesenchymal Stem and Stromal Cells Harness Macrophage-Derived Amphiregulin to 
      Maintain Tissue Homeostasis.
PG  - 3806-3820.e6
LID - S2211-1247(20)30230-8 [pii]
LID - 10.1016/j.celrep.2020.02.062 [doi]
AB  - 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 macrophage 
      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.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Ko, Jung Hwa
AU  - Ko JH
AD  - Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research 
      Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 
      03080, Korea.
FAU - Kim, Hyeon Ji
AU  - Kim HJ
AD  - Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research 
      Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 
      03080, Korea.
FAU - Jeong, Hyun Jeong
AU  - Jeong HJ
AD  - Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research 
      Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 
      03080, Korea.
FAU - Lee, Hyun Ju
AU  - Lee HJ
AD  - Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research 
      Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 
      03080, Korea.
FAU - Oh, Joo Youn
AU  - Oh JY
AD  - Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research 
      Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 
      03080, Korea; Department of Ophthalmology, Seoul National University College of 
      Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Electronic address: 
      jooyounoh77@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Amphiregulin)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Amphiregulin/*metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents/metabolism
MH  - Autoimmune Diseases/prevention & control
MH  - Cell Polarity
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/metabolism
MH  - Epithelium, Corneal/cytology
MH  - ErbB Receptors/metabolism
MH  - Extracellular Vesicles/metabolism
MH  - *Homeostasis
MH  - Humans
MH  - Macrophages/cytology/*metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - *Organ Specificity
MH  - Phagocytosis
MH  - Phenotype
MH  - Receptors, Prostaglandin E, EP4 Subtype/metabolism
MH  - Retinitis/prevention & control
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Th1 Cells/immunology
MH  - Transcription, Genetic
OTO - NOTNLM
OT  - amphiregulin
OT  - autoimmune uveoretinitis
OT  - corneal epithelial stem cell
OT  - extracellular vesicle
OT  - homeostasis
OT  - macrophage
OT  - mesenchymal stem and stromal cell
OT  - phagocytosis
OT  - prostaglandin E2
OT  - regulatory T cell
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2020/03/19 06:00
MHDA- 2021/03/24 06:00
CRDT- 2020/03/19 06:00
PHST- 2019/10/03 00:00 [received]
PHST- 2020/01/12 00:00 [revised]
PHST- 2020/02/14 00:00 [accepted]
PHST- 2020/03/19 06:00 [entrez]
PHST- 2020/03/19 06:00 [pubmed]
PHST- 2021/03/24 06:00 [medline]
AID - S2211-1247(20)30230-8 [pii]
AID - 10.1016/j.celrep.2020.02.062 [doi]
PST - ppublish
SO  - Cell Rep. 2020 Mar 17;30(11):3806-3820.e6. doi: 10.1016/j.celrep.2020.02.062.