Possible association of decreased serum CXCL14 levels with digital ulcers in patients with systemic sclerosis.

CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T-helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17-skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2-skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.