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Increased circulating levels of interleukin 33 in systemic sclerosis correlate with early disease stage and microvascular involvement
  1. Mirko Manetti1,2,
  2. Serena Guiducci2,
  3. Claudia Ceccarelli2,
  4. Eloisa Romano2,
  5. Silvia Bellando-Randone2,
  6. Maria Letizia Conforti2,
  7. Lidia Ibba-Manneschi1,
  8. Marco Matucci-Cerinic2
  1. 1Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy
  2. 2Department of Biomedicine, Division of Rheumatology, AOUC, and Excellence Centre for Research, Transfer and High Education DENOthe, University of Florence, Florence, Italy
  1. Correspondence to Dr Mirko Manetti, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Viale G. B. Morgagni 85, 50134 Florence, Italy; mirkomanetti{at}yahoo.it

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Early activation/damage of endothelial cells and multiple profibrotic T helper type 2 (Th2)-associated cytokines play an important role in the pathogenesis of systemic sclerosis (SSc).1

Interleukin 33 (IL-33) was recently identified as a member of the IL-1 family and a ligand for the orphan receptor ST2L, which mediates the action of IL-33 on polarised Th2 lymphocytes and other leucocyte subsets, and tissue-resident cells, such as vascular endothelial cells and fibroblasts/myofibroblasts.2 IL-33 has been shown to induce IL-13-dependent cutaneous fibrosis and stimulate angiogenesis and vascular permeability.3 4 In healthy human tissues IL-33 protein is constitutively highly expressed in the nuclei of resting endothelial cells, but rapidly lost upon angiogenic or proinflammatory activation.2 Indeed, IL-33 is thought to function as an endogenous ‘alarmin’ that is rapidly released after endothelial cell damage to alert the cells of the innate and adaptive immune system.2

Recently, we have shown that microvascular endothelial cells in inflamed skin from patients with early-stage SSc lacked or had decreased nuclear IL-33 protein expression.5 Instead, IL-33 transcript levels were even upregulated suggesting that, …

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