EXTENDED REPORT

Up regulated expression of fractalkine/CX₃CL1 and CX₃CR1 in patients with systemic sclerosis

M Hasegawa¹, S Sato¹, T Echigo¹, Y Hamaguchi¹, M Yasui², K Takehara¹

¹ Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
² Department of 3rd Internal Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

Correspondence to:
Correspondence to:
Assistant Professor M Hasegawa
Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan; minoruha{at}derma.m.kanazawa-u.ac.jp

Background: Fractalkine expressed on endothelial cells mediates activation and adhesion of leucocytes expressing its receptor, CX₃CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX₃CR1.

Objective: To determine the role of fractalkine and its receptor in systemic sclerosis (SSc) by assessing their expression levels in patients with this disease.

Methods: The expression of fractalkine and CX₃CR1 in the skin and lung tissues was immunohistochemically examined. Circulating soluble fractalkine levels were examined by enzyme linked immunosorbent assay (ELISA). Blood samples from patients with SSc were stained for CX₃CR1 with flow cytometric analysis.

Results: CX₃CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX₃CR1, including monocytes/macrophages, were increased in the lesional skin and lung tissues from patients with diffuse cutaneous SSc. Fractalkine was strongly expressed on endothelial cells in the affected skin and lung tissues. Soluble fractalkine levels were significantly raised in sera and were associated with raised erythrocyte sedimentation rates, digital ischaemia, and severity of pulmonary fibrosis.

Conclusions: Up regulated expression of fractalkine and CX₃CR1 cooperatively augments the recruitment of mononuclear cells expressing CX₃CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.

Abbreviations: Ab, antibody; dSSc, diffuse cutaneous SSc; ELISA, enzyme linked immunosorbent assay; FKN, fractalkine; lSSc, limited cutaneous SSc; mTSS, modified Rodnan total skin thickness score; NK, natural killer; PBMC, peripheral blood mononuclear cells; SSc, systemic sclerosis; TLCO, carbon monoxide transfer factor; TNF, tumour necrosis factor; VC, vital capacity

Keywords: fractalkine; CX3CR1; systemic sclerosis; chemokines

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