Systemic sclerosis articles within Nature Communications

Featured

• Article
  31 January 2024 | Open Access

  GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region

  Here, the authors identify six risk SNPs for systemic sclerosis by performing GWAS on Japanese patients and meta-analyzing Japanese and European GWAS datasets. Downstream analyses indicate that B cells contribute to pathogenesis.

  • Yuki Ishikawa
  • , Nao Tanaka
  •  & Chikashi Terao

• Article
  26 October 2022 | Open Access

  Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs

  A20 gene variants are linked with systemic sclerosis (SS), but the mechanisms are unclear. Here, the authors show that A20 expression is reduced in SS skin and lungs, that its ablation in mice induces SS, and that show that fibrosis can be ameliorated by induction of A20.

  • Wenxia Wang
  • , Swarna Bale
  •  & John Varga

• Article
  20 July 2021 | Open Access

  TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy

  Uncontrolled activation of fibroblasts contributes to tissue fibrosis and organ dysfunction. Here the authors demonstrate that the epigenetic control of autophagy is disturbed by a TGFβ-dependent downregulation of MYST1 in systemic sclerosis patients. Restoration of the epigenetic control of autophagy reduces fibroblast activation and ameliorates fibrotic tissue remodeling.

  • Ariella Zehender
  • , Yi-Nan Li
  •  & Jörg H. W. Distler

• Article
  19 July 2021 | Open Access

  Myofibroblast transcriptome indicates SFRP2^hi fibroblast progenitors in systemic sclerosis skin

  Myofibroblasts drive fibrosis in systemic sclerosis (SSc), but the cellular progenitors are unknown. Utilizing single cell RNA-sequencing, the authors show that SSc dermal myofibroblasts arise in a two-step process from SFRP2/DPP4-expressing progenitors and implicate upstream transcription factors.

  • Tracy Tabib
  • , Mengqi Huang
  •  & Robert Lafyatis

• Article
  31 October 2019 | Open Access

  GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

  Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

  • Elena López-Isac
  • , Marialbert Acosta-Herrera
  •  & Javier Martin

• Article
  01 May 2019 | Open Access

  CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis

  CXCL4 is an inflammatory chemokine signaling through CXCR3 receptor. Here the authors show a CXCR3-independent function of CXCL4: it forms liquid crystals with DNA, potentiating mammalian and bacterial DNA recognition by TLR9, thereby amplifying interferon-a production in systemic sclerosis.

  • Roberto Lande
  • , Ernest Y. Lee
  •  & Loredana Frasca

• Article
  08 March 2019 | Open Access

  Targeting of dermal myofibroblasts through death receptor 5 arrests fibrosis in mouse models of scleroderma

  Dermal myofibroblasts are responsible for fibrosis development in scleroderma. Here the authors show that a bioengineered recombinant human TRAIL ligand reverses established fibrosis in mouse models of scleroderma by targeting the death receptor 5 and inducing apoptosis of myofibroblasts.

  • Jong-Sung Park
  • , Yumin Oh
  •  & Seulki Lee

• Article
  24 October 2017 | Open Access

  Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis

  STAT3 is a transcription factor that is activated in fibrotic diseases such as systemic sclerosis. Here the authors show that STAT3 is the converging point for multiple pro-fibrotic signalling pathways, and that its genetic ablation or inhibition ameliorate skin fibrosis in mouse models.

  • Debomita Chakraborty
  • , Barbora Šumová
  •  & Jörg H. W. Distler

• Article
  20 October 2017 | Open Access

  PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis

  Although protein tyrosine kinases are being explored as antifibrotic agents for the treatment of systemic sclerosis, little is known about the function of counteractive protein tyrosine phosphatases in this context. Here, the authors show that PTP4A1 is highly expressed by fibroblasts from patients with systemic sclerosis and promotes TGFβ activity via SRC–ERK–SMAD3 signaling.

  • Cristiano Sacchetti
  • , Yunpeng Bai
  •  & Nunzio Bottini

• Article
  03 June 2016 | Open Access

  Tenascin-C drives persistence of organ fibrosis

  Systemic sclerosis (SSc) is a fibrotic disease affecting multiple organs. Here the authors use patient samples plus mouse studies to show a central role for tenascin C as a TLR4 activator responsible for persistence of fibrosis in the context of SSc and SSc-like disease.

  • Swati Bhattacharyya
  • , Wenxia Wang
  •  & John Varga

• Article | 12 December 2014

  Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis

  Systemic sclerosis (SSc) is an incurable disease of unknown cause, characterized by vasculopathy, autoimmunity and fibrosis. Here the authors show that simultaneous decrease in two transcription factors, KLF5 and Fli1, underlies SSc development in mice and represents a signature trait of SSc patients.

  • Shinji Noda
  • , Yoshihide Asano
  •  & Shinichi Sato