title: Potential involvement of the IL-33-ST2 axis in the pathogenesis of primary Sjogren's syndrome.
abstract: OBJECTIVE
  To investigate the role of the interleukin (IL)-33-ST2 axis in the pathophysiology of primary Sjögren's syndrome (pSS).
  
  
  METHODS
  Serum levels of IL-33 and sST2 were determined by ELISA. The expression of IL-33 and ST2 was investigated in salivary glands (SG) by immunohistochemistry. PBMC were isolated and stimulated with IL-33, IL-12 and IL-23 and the cytokine profile response was examined by flow cytometry. Intracellular cytokine detection of IFNγ and IL-17 was performed by flow cytometry.
  
  
  RESULTS
  Serum IL-33 and sST2 levels were increased in pSS patients compared with controls and patients with systemic lupus erythematosus. Expression of IL-33 was upregulated in SG with Chisholm scores of 2 and 3 of pSS patients but comparable with controls for SG with Chisholm score of 4. ST2 expression in SG was downregulated in pSS patients. IL-33 at different concentrations did not increase the secretion of pro-inflammatory cytokines but acted synergistically with IL-12 and IL-23 to promote IFNγ production. NK and NKT cells were identified as main producers of IFNγ in vitro and were found in SG of pSS patients.
  
  
  CONCLUSIONS
  IL-33 is released in pSS, and acts with IL-12 and IL-23 to favour the secretion of IFNγ by NK and NKT cells.
authors.affiliation: Department of Rheumatology and Physical Medicine, Hôpital Erasme, Université Libre de Bruxelles, , Brussels, Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.forename: Charles
authors.initials: C
authors.lastname: Nicaise
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ena
authors.forename: Liliane
authors.initials: L
authors.lastname: Schandéné
authors.forename: Joanne
authors.initials: J
authors.lastname: Rasschaert
authors.forename: Iuliana
authors.initials: I
authors.lastname: Popescu
authors.forename: Valérie
authors.initials: V
authors.lastname: Gangji
authors.forename: Muhammad S
authors.initials: MS
authors.lastname: Soyfoo
mesh_terms: D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000209:etiology / Q000378:metabolism*
chemical_list: C573415:IFNG protein, human; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D020381:Interleukin-17; D053759:Interleukin-23; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Autoimmunity; Cytokines; Inflammation; Sjögren's Syndrome