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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.
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Research Article Dermatology Immunology Article has an altmetric score of 95

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

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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

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Figure 6

LTβR signaling maintains ADSCs in the systemic sclerosis–GVHD model of skin fibrosis.

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LTβR signaling maintains ADSCs in the systemic sclerosis–GVHD model of s...
Congenic (control) or B10.D2 (GVHD) splenocytes were adoptively transferred into BALB/c Rag2–/– mice 22–23 days before sacrifice. Back skin was analyzed. (A) Representative H&E-stained sections. Scale bars: 100 μm. (B) Dermal and DWAT thicknesses. (A and B) n = 3 mice per condition over 2 experiments. (C) ADSC numbers per 8-mm punch. (D) Geometric mean fluorescence intensity (MFI) of PDPN on ADSCs. (E) DC numbers per punch. (C–E) n = 6–7 mice per condition over 4 experiments. (F) Effect of LTβR-Ig on ADSC numbers per punch in systemic sclerosis–GVHD mice. Control or LTβR-Ig (100 μg) was given on day 20 after GVHD induction, and animals were sacrificed on day 22. n = 3 mice per condition over 2 experiments. *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)

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