Expression of type III interferons (IFNλs) and their receptor in Sjögren's syndrome.
Type III interferons (IFNs) or IFN-λs (IFN-λ1/IL29, IFN-λ2/interleukin (IL)-28A and IFN-λ3/IL-28B) consist of a recently identified group of IFNs, implicated initially in several human diseases, including cancer and autoimmunity. In this study, we sought to investigate the expression of type III IFNs and their common receptor IFN-λR1/IL-28Ra in Sjögren's syndrome (SS). Type III IFN expression was examined in minor salivary gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC) from SS patients and sicca-complaining controls. All type III IFN family members were detected in ductal and acinar epithelia of MSGs from both SS patients and sicca controls. IFN-λ2/IL-28A and IFN-λ3/IL-28B were also expressed in infiltrating mononuclear cells. In SS patients with intermediate MSG lesions, the epithelial expression of IFN-λ2/IL-28A was more intense compared to sicca controls (P < 0·05). The receptor IFN-λR1/IL-28Ra was detected in all types of cells except fibroblasts, and was exceptionally strong in plasmatocytoid dendritic cells, indicating that they are susceptible to type III IFN-mediated regulation. In the periphery, only IFN-λ1/IL-29 was detected in the sera and was elevated significantly in SS patients with intermediate MSG inflammatory lesions compared to sicca controls (P = 0·0053). None of the type III IFNs was expressed constitutively in resting SGECs; they were all induced readily by TLR-3 stimulation, suggesting that the in-situ epithelial expression can be attributed to local microenvironment. Type III IFNs are expressed in MSGs in a similar pattern to type I IFNs and their expression is probably subjected to micro-environmental regulation, suggesting that they are implicated in the inflammatory processes occurring in the affected exocrine glands.
Pathophysiology Department, National and Kapodistrian University of Athens, Athens, Greece.|Academic Joint Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.
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Apostolou
Pathophysiology Department, National and Kapodistrian University of Athens, Athens, Greece.|Academic Joint Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.
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Kapsogeorgou
Pathophysiology Department, National and Kapodistrian University of Athens, Athens, Greece.|Academic Joint Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.
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Konsta
2nd Otolaryngology Department, 'Attikon' University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
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Giotakis
Department of Immunology, Center for Clinical and Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.
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Saridaki
Department of Immunology, Center for Clinical and Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.
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Andreakos
Pathophysiology Department, National and Kapodistrian University of Athens, Athens, Greece.|Academic Joint Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.
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Tzioufas
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D055815:Young Adult; D000096743:Interferon gamma Receptor
D015415:Biomarkers; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D051196:Toll-Like Receptor 3; D000096743:Interferon gamma Receptor
TLRs; autoimmunity; cytokines; inflammation