Connective tissue diseases

  • Article
    | Open Access

    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
    | Open Access

    Type I interferon drives autoimmune pathology in SLE and has been assumed to come predominantly from plasmacytoid dendritic cells (pDCs). Here, the authors show that prior to the onset of SLE, pDCs lose multiple immunogenic functions and, instead, non-hematopoietic cells such as keratinocytes are a major source of type I interferons.

    • Antonios Psarras
    • , Adewonuola Alase
    •  & Edward M. Vital
  • Article
    | Open Access

    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
    | Open Access

    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
    | Open Access

    Antiphospholipid syndrome is characterised by increased neutrophil extracellular trap formation (NETosis) and, consequently, increased thrombotic events. Here Ali et al. show that treatment with adenosine receptor agonists suppresses NETosis and venous thrombosis in mouse models of antiphospholipid syndrome.

    • Ramadan A. Ali
    • , Alex A. Gandhi
    •  & Jason S. Knight
  • Article
    | Open Access

    Hyperactivation of TGFβ signaling is a common feature of fibrotic diseases. Here the authors show that genetic or pharmacologic inactivation of the tyrosine phosphatase SHP2 prevents TGFβ-induced JAK2/STAT3 signaling, inhibits fibroblast activation and exerts potent anti-fibrotic effects.

    • Ariella Zehender
    • , Jingang Huang
    •  & Jörg H. W. Distler
  • Article
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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 |

    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