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Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints
  1. Lode Melis1,
  2. Liesbet Van Praet1,2,
  3. Hanspeter Pircher3,
  4. Koen Venken1,
  5. Dirk Elewaut1,2
  1. 1Faculty of Medicine and Health Sciences, Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent, Belgium
  2. 2Faculty of Medicine and Health Sciences, Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
  3. 3Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg, Germany
  1. Correspondence to Dr Dirk Elewaut, Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, 0K12IB, De Pintelaan 185, Ghent 9000, Belgium; dirk.elewaut{at}


Objectives Killer cell lectin-like receptor G1 (KLRG1) is an NK cell marker also expressed on T cells showing an immunosenescent phenotype. KLRG1 binding to its ligand E-cadherin inhibits functional responses. It was recently shown that soluble E-cadherin (sE-cadherin) also influences KLRG1 signalling, although its involvement in arthritis is unknown. Our goal was to evaluate the contribution of KLRG1+ T cells to synovitis.

Methods Paired peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 21 patients with spondyloarthritis (SpA) or rheumatoid arthritis (RA), eight with crystal-induced arthritis and 10 controls were obtained. T cells were characterised for KLRG1 expression directly ex vivo, while TNF-α/IFN-γ production was assessed after polyclonal stimulation. Assays of chemotaxis response towards SF were conducted. Additionally, sE-cadherin levels in our paired samples were determined. Moreover, TNF-α/IFN-γ production by antigen-specific T cells was evaluated in the presence of sE-cadherin.

Results KLRG1+ T cells were enriched in SF as opposed to PB of SpA and RA patients, which contrasts with results obtained in crystal-induced arthritides. KLRG1+ T cells were more functionally active as opposed to KLRG1 T cells and migrated preferentially towards SpA and RA SF. sE-cadherin levels were higher in SF versus plasma. The presence of sE-cadherin enhanced the number of KLRG1+ CD4+ T cells able to produce TNF-α but not IFN-γ.

Conclusions sE-cadherin contributes to the local proinflammatory environment in the joint by favouring TNF-α production by KLRG1+ CD4+ T cells. This pathway seems to be operational in both SpA and RA, but not in crystal-induced arthritis.

  • Arthritis
  • Synovial fluid
  • TNF-alpha
  • Spondyloarthritis
  • Rheumatoid Arthritis

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