IL-34 is overexpressed in the inflamed salivary glands of patients with Sjogren's syndrome and is associated with the local expansion of pro-inflammatory CD14(bright)CD16+ monocytes

Abstract

Objectives: To investigate the expression of IL-34 in labial salivary glands (LSGs) of patients with primary SS (p-SS) and its role in inducing a pro-inflammatory monocyte phenotype.

Methods: LSG biopsies were obtained from 20 patients with p-SS and 10 patients with non-Sjögren's sicca syndrome (n-SS). The expression of IL-34, IL-1β, TNF-α, IL-17 and IL-23 was assessed by real-time PCR. IL-34 expression was also investigated in LSGs by immunohistochemistry. The frequencies of subpopulations of CD14(+) monocytes were evaluated by flow cytometry among isolated mononuclear cells from peripheral blood and salivary glands from both patients and controls. The role of recombinant IL-34 on isolated peripheral blood mononuclear cells was also evaluated.

Results: IL-34 m-RNA was overexpressed in the inflamed salivary glands of p-SS and associated with increased expression of TNF-α, IL-1β, IL-17 and IL-23p19. The increased expression of IL-34 was confirmed by immunohistochemistry in paraffin-embedded salivary glands from p-SS patients. IL-34 expression was accompanied by the expansion of pro-inflammatory CD14(bright)CD16(+) monocytes in the salivary glands. In vitro stimulation of peripheral blood mononuclear cells with IL-34 induced the expansion of both CD14(+)CD16(-) cells and CD14(bright)CD16(+) cells in p-SS and non-SS subjects.

Conclusion: IL-34 seems to be involved in the pathogenesis of salivary gland inflammation in p-SS.

Keywords: Sjögren’s syndrome; interleukin-34; monocytes.