ResearchIn-Press PreviewCell biology Open Access | 10.1172/jci.insight.160977
1Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, United States of America
2Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, United States of America
3Departments of Dermatology and Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, United States of America
4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
5Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chciago, United States of America
Find articles by Corano-Scheri, K. in: JCI | PubMed | Google Scholar
1Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, United States of America
2Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, United States of America
3Departments of Dermatology and Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, United States of America
4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
5Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chciago, United States of America
Find articles by Liang, X. in: JCI | PubMed | Google Scholar
1Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, United States of America
2Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, United States of America
3Departments of Dermatology and Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, United States of America
4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
5Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chciago, United States of America
Find articles by Dalal, V. in: JCI | PubMed | Google Scholar |
1Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, United States of America
2Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, United States of America
3Departments of Dermatology and Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, United States of America
4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
5Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chciago, United States of America
Find articles by Le Poole, I. in: JCI | PubMed | Google Scholar |
1Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, United States of America
2Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, United States of America
3Departments of Dermatology and Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, United States of America
4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
5Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chciago, United States of America
Find articles by Varga, J. in: JCI | PubMed | Google Scholar
1Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, United States of America
2Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, United States of America
3Departments of Dermatology and Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, United States of America
4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
5Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chciago, United States of America
Find articles by Hayashida, T. in: JCI | PubMed | Google Scholar |
Published September 22, 2022 - More info
We previously reported that Smad Anchor for Receptor Activation (SARA) plays a critical role in maintaining epithelial cell phenotype. Here, we show that SARA suppresses myofibroblast precursor transdifferentiation in a mouse model of scleroderma. Mice overexpressing SARA specifically in PDGFRβ+ pericytes and pan-leukocytes (SARATg) developed significantly less skin fibrosis in response to bleomycin injection compared to wild-type littermates (SARAWT).Single cell RNASeq analysis of skin PDGFRβ+ cells implicated pericyte subsets assuming myofibroblast characteristics under fibrotic stimuli, and SARA overexpression blocked the transition. In addition, a cluster that expresses molecules associated with Th2 cells and macrophage activation was enriched in SARAWT, but not in SARATg mouse, after bleomycin treatment. Th2- specific Il-31 expression was increased in skin of the bleomycin-treated SARAWT mice, and scleroderma patients. Receptor-ligand analyses indicated that lymphocytes mediate pericyte transdifferentiation in SARAWT mice, while with SARA overexpression the myofibroblast activity of pericytes was suppressed. Together, these data suggest a novel crosstalk between myofibroblast precursors and immune cells in the pathogenesis of SSc, for which SARA plays a critical role.