title: Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18.
abstract: The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls . The effect of recombinant IL-18 and IL-22 on peripheral blood mononuclear cells (PBMCs) from pSS and nSCS was studied by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR). MSGs of pSS and NHL were characterized by an imbalance between IL-22 and IL-22BP protein expression, with IL-18 and IL-22BP being expressed in a mutually exclusive manner and IL-18 and IL-22R1 being correlated directly. Aberrant expression of IL-22R1, induced by IL-18, was observed only among tissue and circulating myeloid cells of pSS patients and macrophages of NHL tissues of pSS patients, but not nSCS. IL-22R1 expression on PBMC of pSS was functional, as its stimulation with recombinant IL-22 significantly up-regulated the expression of STAT-3, IL-17 and IL-22. An IL-18-dependent aberrant expression of IL-22R1 on cells of haematopoietic origin seems to be a specific immunological signature of patients with pSS and pSS-associated lymphomas.
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Palermo, Italy.|Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Azienda Ospedaliera Ospedali riuniti Villa Sofia-Cervello, Anatomia Patologica, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bombardieri
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Raimondo
authors.affiliation: Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Carubbi
authors.affiliation: Azienda Ospedaliera Ospedali riuniti Villa Sofia-Cervello, Anatomia Patologica, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cannizzaro
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sireci
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Dieli
authors.affiliation: Dipartimento di discipline Chirurgiche, Università di Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Campisi
authors.affiliation: Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Giacomelli
authors.affiliation: Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Leo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Triolo
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology* / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D061251:Primary Cell Culture; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology; D012793:Sialadenitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D020382:Interleukin-18; D007378:Interleukins; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C433253:IL22RA2 protein, human; C494086:STAT3 protein, human; C415369:interleukin-22 receptor
keywords: IL-18; IL-22; IL-22BP; IL-22R1; Sjögren's syndrome; non-Hodgkin lymphoma