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

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 5

DC-derived LTβ maintains ADSC survival in BLM-induced fibrosis.

Options: View larger image (or click on image) Download as PowerPoint
DC-derived LTβ maintains ADSC survival in BLM-induced fibrosis.
(A) Repr...
(A) Representative histograms of LTβ staining in skin CD11b– DCs (left) and CD11b+ DCs (right) from mice treated with BLM for 21–25 days. n = 6 WT mice and 3 Ltb–/– mice over 3 experiments. (B–D) zDCDTR/+/WT→WT mixed chimeras (WT) or zDCDTR/+/Ltb–/–→WT mixed chimeras (Ltb–/– ) were injected with BLM over 21 to 22 days, with PBS or DT for the final 1–2 days before skin analysis. (B) DC numbers enumerated by bone marrow donor genotype. Numbers are reported per 8-mm punch. n = 7 chimeras over 5 experiments. (C) ADSC numbers. Left: absolute numbers per punch; right: normalized to PBS groups. n = 8–9 chimeras per condition over 7 experiments. (D) Percentage of ADSCs that are TUNEL+. n = 5 chimeras per condition over 5 experiments. (E and F) zDCDTR/+ chimeras were treated with BLM over 22 days, with PBS or DT for the final 2 days, and with 20 μg anti-LTβR or isotype control 6 hours before the first dose of PBS or DT. n = 4 chimeras per condition over 4 experiments. PBS and DT experiments were performed separately using different batches of chimeras. (E) ADSC numbers. Left: absolute numbers per punch; right: normalized. (F) Percentage of ADSCs that are TUNEL+. (G and H) CD31–CD45–PDPN+DAPI– cell counts from murine ADSC cultures that were serum-starved and treated with the indicated cells and reagents. (G) Effect on ADSC survival of DCs without or with LTβR-Ig for 48 hours. (H) Effect on ADSC survival of isotype control or agonist anti-LTβR for 48 hours. (I) CD31–CD45–PDPN+DAPI– cell counts from human primary ADSC cultures that were serum-starved and treated with isotype control or agonist anti-LTβR for 48 hours. (G–I) Each symbol represents 1 of 3 to 5 experiments with 1 to 3 replicate wells per experiment. *P < 0.05, **P < 0.01, ***P < 0.001 using 2-tailed unpaired Student’s t test. Error bars depict the SEM.

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

Sign up for email alerts