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The IL-1-like cytokine IL-33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis
Annals of Rheumatic Diseases, 10/08/09

Manetti M et al. – IL-33 and ST2 are abnormally expressed in SSc. In early SSc, upon EC activation/damage, IL-33 may be mobilised from ECs to signal through ST2 in key pro-fibrotic players, such as inflammatory/immune cells and fibroblasts/myofibroblasts

• Skin biopsies obtained from 30 SSc patients (15 early/15 late stage) and 10 healthy subjects
• Lung, kidney, heart, esophagus, stomach, placenta biopsies and bronchoalveolar lavage cells from SSc patients and controls also analysed
• IL-33/ST2 expression investigated by immunohistology, confocal immunofluorescence microscopy, Western blotting and RT-PCR

• In control skin, constitutive nuclear IL-33 protein expression found in dermal ECs and keratinocytes, while ST2 weakly expressed in ECs and fibroblasts
• ECs, perivascular infiltrating mast cells, CD68-positive macrophages, CD3-positive T cells, CD20-positive B cells, and activated fibroblasts/myofibroblasts exhibited strong ST2 expression
• In late SSc skin, IL-33 was constitutively found in most ECs, while ST2 immunostaining was weaker
• In early SSc, loss of endothelial IL-33 protein and overexpression of ST2 involved all affected organs
• Dermal and pulmonary fibroblasts showed IL-33 expression in SSc

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