Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis
Jennifer J. Chia, … , Jessica K. Gordon, Theresa T. Lu
Jennifer J. Chia, … , Jessica K. Gordon, Theresa T. Lu
Published October 10, 2016
Citation Information: J Clin Invest. 2016;126(11):4331-4345. https://doi.org/10.1172/JCI85740.
View: Text | PDF
Research Article Dermatology Immunology Article has an altmetric score of 95

Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis

  • Text
  • PDF
Abstract

Scleroderma is a group of skin-fibrosing diseases for which there are no effective treatments. A feature of the skin fibrosis typical of scleroderma is atrophy of the dermal white adipose tissue (DWAT). Adipose tissue contains adipose-derived mesenchymal stromal cells (ADSCs) that have regenerative and reparative functions; however, whether DWAT atrophy in fibrosis is accompanied by ADSC loss is poorly understood, as are the mechanisms that might maintain ADSC survival in fibrotic skin. Here, we have shown that DWAT ADSC numbers were reduced, likely because of cell death, in 2 murine models of scleroderma skin fibrosis. The remaining ADSCs showed a partial dependence on dendritic cells (DCs) for survival. Lymphotoxin β (LTβ) expression in DCs maintained ADSC survival in fibrotic skin by activating an LTβ receptor/β1 integrin (LTβR/β1 integrin) pathway on ADSCs. Stimulation of LTβR augmented the engraftment of therapeutically injected ADSCs, which was associated with reductions in skin fibrosis and improved skin function. These findings provide insight into the effects of skin fibrosis on DWAT ADSCs, identify a DC-ADSC survival axis in fibrotic skin, and suggest an approach for improving mesenchymal stromal cell therapy in scleroderma and other diseases.

Authors

Jennifer J. Chia, Tong Zhu, Susan Chyou, Dragos C. Dasoveanu, Camila Carballo, Sha Tian, Cynthia M. Magro, Scott Rodeo, Robert F. Spiera, Nancy H. Ruddle, Timothy E. McGraw, Jeffrey L. Browning, Robert Lafyatis, Jessica K. Gordon, Theresa T. Lu

×

Figure 3

DCs are localized in the DWAT of homeostatic and fibrotic skin.

Options: View larger image (or click on image) Download as PowerPoint
DCs are localized in the DWAT of homeostatic and fibrotic skin.
(A) DC n...
(A) DC numbers in unfractionated skin or indicated skin fraction as assessed by flow cytometry. Numbers are reported per 8-mm punch. n = 5–7 mice per condition over 3 to 4 experiments. (B and C) Back skin from WT mice or zDCGFP/GFP→WT chimeras (zDCGFP/GFP chimera) was stained for GFP (red) and DAPI (blue). Representative of n = 2 mice per condition. (B) Representative images. Dashed line indicates division between dermis and DWAT. (C) GFP+ cell numbers (left) and GFP+ cells per area (right) in the dermis and DWAT of zDCGFP/GFP chimeras. Each symbol represents a field; similarly shaded symbols are from the same chimera. (D) DC numbers per punch as assessed by flow cytometry in WT mice treated with PBS or BLM as indicated. n = 4–8 over 2 to 4 experiments. (E and F) zDCGFP/GFP chimeras were treated with BLM for 21 days, and then back skin was stained for GFP (red) and DAPI (blue). n = 2 chimeras. (E) Representative image. Dashed line indicates division between dermis and DWAT. (F) GFP+ cell numbers (left) and GFP+ cells per area (right). Each symbol represents a field; similarly shaded symbols are from the same chimera. HPF, high-power field. (G and H) Human systemic sclerosis (SSc) lesional skin sections stained for CD1c (red), perilipin (white), and DAPI (blue). n = 3 individuals. (G) Representative images. Orange particles are autofluorescent and nonspecific. Insets highlight nucleated CD1c+ cells. (H) CD1c+ cells per area. Each symbol represents a field; similarly shaded symbols are from the same patient. Scale bars: 20 μm. *P < 0.05, **P < 0.01, ***P < 0.001 using 2-tailed unpaired Student’s t test. Error bars depict the SD in D and the SEM in other graphs.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 12 news outlets
Blogged by 1
Posted by 3 X users
Referenced in 1 patents
On 1 Facebook pages
64 readers on Mendeley
See more details