PMID- 29898959
OWN - NLM
STAT- MEDLINE
DCOM- 20190705
LR  - 20190705
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 201
IP  - 2
DP  - 2018 Jul 15
TI  - Myeloid Cell-Restricted STAT3 Signaling Controls a Cell-Autonomous Antifibrotic 
      Repair Program.
PG  - 663-674
LID - 10.4049/jimmunol.1701791 [doi]
AB  - Myeloid cells can be beneficial as well as harmful in tissue regenerative 
      responses. The molecular mechanisms by which myeloid cells control this critical 
      decision of the immune system are not well understood. Using two different models 
      of physiological acute or pathological chronic skin damage, in this study we 
      identified myeloid cell-restricted STAT3 signaling as important and an injury 
      context-dependent regulator of skin fibrosis. Targeted disruption of STAT3 
      signaling in myeloid cells significantly accelerated development of pathological 
      skin fibrosis in a model of chronic bleomycin-induced tissue injury, whereas the 
      impact on wound closure dynamics and quality of healing after acute excision skin 
      injury was minor. Chronic bleomycin-mediated tissue damage in control mice 
      provoked an antifibrotic gene signature in macrophages that was characterized by 
      upregulated expression of IL-10, SOCS3, and decorin. In contrast, in 
      STAT3-deficient macrophages this antifibrotic repair program was abolished 
      whereas TGF-beta1 expression was increased. Notably, TGF-beta1 synthesis in cultured 
      control bone marrow-derived macrophages (BMDMs) was suppressed after IL-10 
      exposure, and this suppressive effect was alleviated by STAT3 deficiency. 
      Accordingly, coculture of IL-10-stimulated control BMDMs with fibroblasts 
      suppressed expression of the TGF-beta1 downstream target connective tissue growth 
      factor in fibroblasts, whereas this suppressive effect was lost by STAT3 
      deficiency in BMDMs. Our findings highlight a previously unrecognized protective 
      role of myeloid cell-specific STAT3 signaling in immune cell-mediated skin 
      fibrosis, and its regulatory pathway could be a potential target for therapy.
CI  - Copyright (c) 2018 by The American Association of Immunologists, Inc.
FAU - Do, Nhu-Nguyen
AU  - Do NN
AD  - Department of Dermatology, University of Cologne, 50937 Cologne, Germany.
FAU - Willenborg, Sebastian
AU  - Willenborg S
AD  - Department of Dermatology, University of Cologne, 50937 Cologne, Germany.
FAU - Eckes, Beate
AU  - Eckes B
AD  - Translational Matrix Biology Group, University of Cologne, 50931 Cologne, 
      Germany.
FAU - Jungst, Christian
AU  - Jungst C
AD  - Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated 
      Diseases, University of Cologne, 50931 Cologne, Germany.
FAU - Sengle, Gerhard
AU  - Sengle G
AD  - Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, 
      Germany.
AD  - Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, 
      Germany; and.
FAU - Zaucke, Frank
AU  - Zaucke F
AUID- ORCID: 0000-0002-7680-9354
AD  - Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopedic University 
      Hospital, Friedrichsheim gGmbh, 60528 Frankfurt/Main, Germany.
FAU - Eming, Sabine A
AU  - Eming SA
AD  - Department of Dermatology, University of Cologne, 50937 Cologne, Germany; 
      sabine.eming@uni-koeln.de.
AD  - Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated 
      Diseases, University of Cologne, 50931 Cologne, Germany.
AD  - Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, 
      Germany; and.
LA  - eng
SI  - ClinicalTrials.gov/NCT00984646
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180613
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Interleukin-10/metabolism
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Cells/*physiology
MH  - Regeneration
MH  - STAT3 Transcription Factor/genetics/*metabolism
MH  - Signal Transduction
MH  - Skin/*pathology
MH  - Skin Diseases/chemically induced/*immunology
MH  - Transcriptome
MH  - Transforming Growth Factor beta/metabolism
MH  - Wound Healing
EDAT- 2018/06/15 06:00
MHDA- 2019/07/06 06:00
CRDT- 2018/06/15 06:00
PHST- 2017/12/27 00:00 [received]
PHST- 2018/05/03 00:00 [accepted]
PHST- 2018/06/15 06:00 [pubmed]
PHST- 2019/07/06 06:00 [medline]
PHST- 2018/06/15 06:00 [entrez]
AID - jimmunol.1701791 [pii]
AID - 10.4049/jimmunol.1701791 [doi]
PST - ppublish
SO  - J Immunol. 2018 Jul 15;201(2):663-674. doi: 10.4049/jimmunol.1701791. Epub 2018 
      Jun 13.