Monocytes and Dendritic Cells in Sjögren’s Syndrome

Sjögren’s Syndrome is an autoimmune disorder with an estimated prevalence of around 3-4% in women. The disease is characterized by lymphocytic infiltration in the salivary and lachrymal glands, leading to decreased salivary and tear flow. Furthermore, patients suffer from extreme fatigue and arthralgia, severely impacting the quality of life. Although both T and B cells are involved in the effector phase of the disease, it is unknown whether the abnormalities in these populations are intrinsic or due to excessive stimulation. We have shown earlier that an accumulation of dendritic cells (DC) is one of the first events in the development of Sjögren’s Syndrome. Since DC are key players in the initiation and perpetuation of immune responses, this is likely to play a role in the pathogenesis of the disease. In this study, we focused on the causes and consequences of the DC accumulation in Sjögren’s Syndrome. The results show that abnormalities occur already in the precursor population of monocytes. An increased number of mature monocytes are present in Sjögren Syndrome patients, and these cells develop into highly activated DC. Furthermore, abnormalities in the processing of fractalkine occur in the salivary gland, which is important in attracting mature monocytes. Together these phenomena contribute to the accumulation of DC in salivary glands. Also the DC themselves are aberrant, in that they lack expression of CCR5, leading to a more pro-inflammatory phenotype. This contributes to the local inflammatory environment and the perpetuation of the immune response. Additionally, plasmacytoid DC in the blood of patients are more activated than in controls which coincides with an increase in type I IFN activity. This may be of importance for the systemic complaints of patients.

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