Dendritic cells, T-cells and epithelial cells: a crucial interplay in immunopathology of primary Sjögren's syndrome

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that is characterized by mononuclear cell infiltration of exocrine glands. T-cells have been shown to play a central role in tissue destruction and regulation of B-cell activity and the production of autoantibodies typifying pSS. Despite the fact that dendritic cells (DCs) are candidate key players in the activation of T- and B-cells in pSS, their contribution has been under evaluated. This manuscript reviews current insights in DC biology and examines literature on the role of DCs in the immunopathology of primary Sjögren's syndrome, focusing on the interplay between dendritic cells, epithelial cells and T-cells.

Keywords::

• dendritic cells
• epithelial cells
• immunopathology
• primary Sjögren's syndrome
• T-cells

Financial & competing interests disclosure

The authors were supported by the Dutch Arthritis Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Dendritic cells (DCs) are candidate key players in primary Sjögren's syndrome (pSS) immunopathology, but have been poorly studied so far.

• Decreased numbers of plasmacytoid DCs and a subset of classical/myeloid DCs (cDCs) are present in the peripheral blood of pSS patients compared with controls. Migration of DCs from the blood to the salivary glands is seen in experimental mouse models for pSS and suggests that enhanced migration from the blood to the salivary glands of pSS patients reflects their low abundance in the circulation compared with healthy controls.

• In the salivary glands of pSS patients, higher numbers of DCs are present compared with controls.

• Plasmacytoid DCs present in pSS salivary gland tissue are thought to produce high levels of IFN-α, a cytokine that stimulates epithelial cells and monocytes to produce B-cell-activating factor, which is involved in stimulating B cells.

• The cDCs in the pSS salivary glands include mature cDCs that can vigorously activate T cells to proliferate and produce proinflammatory cytokines, including IFN-γ that could strongly contribute to the observed interferon signature in pSS.

• Epithelial cells in the salivary gland produce factors that attract DCs and T cells and can activate T cells and B cells.

• T-cells can activate epithelial cells and DCs via cell–cell contact and by production of proinflammatory cytokines.

• The interplay between epithelial cells, cDCs, T cells and B-cells may be critical in immunopathology of pSS.

Notes