title: Interleukin-36α axis is modulated in patients with primary Sjögren's syndrome.
abstract: The aim of this study was to investigate the expression of the interleukin (IL)-36 axis in patients with primary Sjögren's syndrome (pSS). Blood and minor labial salivary glands (MSG) biopsies were obtained from 35 pSS and 20 non-Sjögren's syndrome patients (nSS) patients. Serum IL-36α was assayed by enzyme-linked immunosorbent assay (ELISA). IL-36α, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19 and expression in MSGs was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and tissue IL-36α and IL-38 expression was also investigated by immunohistochemistry (IHC). αβ and γδ T cells and CD68(+) cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. IL-36α was over-expressed significantly in the serum and in the salivary glands of pSS. Salivary gland IL-36α expression was correlated with the expression levels of IL-17, IL-22 and IL-23p19. IL-38, that acts as inhibitor of IL-36α, was also up-regulated in pSS. αβ(+) CD3(+) T cells and CD68(+) cells were the major source of IL-36α in minor salivary glands of pSS. γδ T cells were not significantly expanded in the salivary glands of pSS but produced more IL-17, as their percentage correlated with the focus score. Higher expression of IL-36α and IL-36R was also demonstrated in γδ T cells isolated from pSS compared to controls. In this study we demonstrate that a significant increase in circulating and tissue levels of IL-36α occurs in pSS patients.
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistiche, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Dipartimento di Oncoematologia, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Sezione di Anatomia Patologica, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Accardo-Palumbo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: UOC di Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università degli Studi di Roma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Alessandri
authors.affiliation: UOC di Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università degli Studi di Roma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Priori
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistiche, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Raimondo
authors.affiliation: UOC di Oculistica, Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Carubbi
authors.affiliation: UOC di Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università degli Studi di Roma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Valesini
authors.affiliation: UOC di Oculistica, Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Giacomelli
authors.affiliation: Dipartimento di Oncoematologia, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Sezione di Anatomia Patologica, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistiche, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Triolo
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000097043:Interleukin-22; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007375:Interleukin-1; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C571243:IL-38 protein, human; C508586:IL36A protein, human; C571244:interleukin-36 receptor, human
keywords: IL-36a; IL-38; IL36RA; Sjögren's syndrome; γδ T cells