title: CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland infiltrates: fractalkine contribution to lymphoid neogenesis in Sjogren's syndrome.
abstract: OBJECTIVE
  Primary SS is an autoimmune disease characterized by chronic lymphocytic inflammation and ectopic germinal centre (GC) formation within salivary glands. Fractalkine (CX3CL1), associated with the pathogenesis of RA, is the sole member of the CX3C chemokine (CK) family and acts as an adhesion and chemotactic molecule. The objectives of this work are to determine to what extent CX3CL1 and its receptor CX3CR1 expression might be altered in salivary glands obtained from patients and to establish whether these CKs might be involved in SS ectopic lymphoneogenesis.
  
  
  METHODS
  We assessed the presence of CX3CL1 protein in sera by ELISA in 21 patients with primary SS, 11 patients with Sicca syndrome (Sicca), 20 RA patients and 10 blood donors. Histological evaluation was performed on sequential sections of salivary gland tissue. Using TaqMan RT-PCR we studied CX3CL1 and CX3CR1 mRNA expression in salivary gland tissues from a molecular point of view.
  
  
  RESULTS
  Increased serum levels of CX3CL1 protein were observed in SS patients compared with controls (P < 0.0001) and in RA patients compared with controls (P < 0.0001), but no difference was found between Sicca patients and controls (P = 0.22). We identified histologically the cells expressing CX3CL1 and CX3CR1 in salivary glands of SS patients and we localized the molecule within tertiary lymphoid structures. Finally, the mRNA levels of the CK and its receptor were up-regulated in SS salivary glands.
  
  
  CONCLUSIONS
  We believe that our findings point to the need for future studies on CX3CL1 and CX3CR1 proteins as contributors to the formation of ectopic GCs and possibly as a new tool in the evaluation and diagnosis of SS.
authors: Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Charterhouse Square, London EC1M 6BQ, UK. e.astorri@qmul.ac.uk.
authors: Elisa
authors: E
authors: Astorri
authors: Rossana
authors: R
authors: Scrivo
authors: Michele
authors: M
authors: Bombardieri
authors: Giovanna
authors: G
authors: Picarelli
authors: Irene
authors: I
authors: Pecorella
authors: Alessandra
authors: A
authors: Porzia
authors: Guido
authors: G
authors: Valesini
authors: Roberta
authors: R
authors: Priori
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000276:immunology*; D002828:Choristoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D012466:Salivary Gland Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012470:Salivary Glands, Minor / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D012333:RNA, Messenger; D019707:Receptors, Chemokine
keywords: Sjögren’s syndrome; fractalkine; germinal centres; salivary glands