AB0043 Impact of fractalkine (cx3cl1) in primary sjogren’s syndrome: its expression in labial salivary gland
Authors: J. H. Lee, J. Lee, S.-M. Jung, Y.-G. Jeong, K.-S. Park, D. C. Jeong, S.-H. Park, S.-K. Kwok
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sjögren's syndrome (SS) in humans is an organ-specific autoimmune disorder characterized by lymphocytic infiltration and destruction of the lacrimal and salivary glands (1). Chemokines are small chemoattractant cytokines that induce leukocyte accumulation at inflammatory sites and modulate inflammatory activities through the recruited cells (2). Fractalkine (CX<sub>3</sub>CL1) is a member of the CX<sub>3</sub>C family. Fractalkine is considered especially important for the recruitment of Th1 type cells and is a strong candidate for directing pathologic mononuclear cell infiltration (3). In mice model, fractalkine was expressed and associated development of autoimmune lesions in lacrimal gland (4). <h3>Objectives</h3> To identify the expression of fractalkine in human salivary gland and serum in SS. To investigate the cell type expressing CX<sub>3</sub>CR1 in peripheral blood mononuclear cell with SS. <h3>Methods</h3> Serum fractalkine level was determined by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical stain was done to compare the expression of fractalkine and CX<sub>3</sub>CR1 between salivary gland of SS and control. The cells to be merged with fractalkine were evaluated by confocal microscopy. Cytokine-stimulated fractalkine expression was quantified by Quantitative real time PCR (QPCR) and ELISA, using A253 cell line. We investigated CX<sub>3</sub>CR1expressing cell in human peripheral blood mononuclear cell (PBMC) by QPCR and flow cytometry. <h3>Results</h3> There was a significantly increased serum fractalkine level in SS compared with control. It showed increased expression in fractalkine and CX<sub>3</sub>CR1 in SS salivary gland rather than control by immunohisto-chemical stain. Fractalkine and CX<sub>3</sub>CR1 positive cell count showed a tendency to increase as higher grade in SS salivary gland. In confocal microscopy, epithelial cell and fractalkine was merged together, but not endothelial cell in SS salivary gland. Only interferon-gamma (IFN-γ) stimulation induced upregualtion of fractalkine expression in A253 cell line, but not interleukin-1beta (IL-1ß) and tumor necrosis fator-alpha (TNF-α). However, CX<sub>3</sub>CR1 expression in PBMC did not show significant difference between SS and control. <h3>Conclusions</h3> Salivary gland of SS expresses high level of fractalkine and CX<sub>3</sub>CR1. Histologic grade is proportional to expression of fractalkine and CX<sub>3</sub>CR1. Main cell of fractalkine production are epithelial cell in SS salivary gland. <h3>References</h3> Fox RI, Robinson CA, Curd JG, Kozin F, Howell FV. Sjogren's syndrome: proposed criteria for classification. <i>Arthritis Rheum.</i>1986;29:577–585 Baggiolini M. Chemokines and leukocyte traffic. <i>Nature.</i> 1998;392:565–568 Teupser D, Pavlides S, Tan M, et al. Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root. <i>Proc Natl Acad Sci U S A.</i>2004;101:17795–17800. Tsubota K, Nishiyama T, Mishima K, Inoue H, Doi T, Hattori Y, et al. The role of fractalkine as an accelerating factor on the autoimmune exocrinopathy in mice. <i>Invest Ophthalmol Vis Sci.</i> 2009;50:4753-60 <h3>Disclosure of Interest</h3> J. H. Lee Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, J. Lee Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, S.-M. Jung Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, Y.-G. Jeong Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, K.-S. Park Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, D. C. Jeong Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, S.-H. Park Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable, S.-K. Kwok Shareholder of: not applicable, Grant/research support from: not applicable, Consultant for: not applicable, Employee of: not applicable, Paid instructor for: not applicable, Speakers bureau: not applicable