Dendritic Cells Maintain Dermal Adipose-derived Stromal Cells in Skin Fibrosis

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2016 Oct 11

PMID 27721238

Citations 33

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

Affiliations

Soon will be listed here.

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.

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