Decrease of blood dendritic cells and increase of tissue-infiltrating dendritic cells are involved in the induction of Sjögren's syndrome but not in the maintenance

Abstract

SummaryWe have demonstrated previously that, in primary Sjögren's syndrome (SS), immature myeloid dendritic cells (DCs) are decreased in blood and mature myeloid DCs are accumulated in salivary glands, suggesting recruitment of the myeloid DCs from blood to salivary glands. To verify whether this finding is universal in patients of not only primary SS but also secondary SS, in this study we analysed the blood DCs of secondary SS patients. We examined 24 secondary SS and 29 primary SS patients. A direct correlation between the decreased number of myeloid DCs and the duration of Sicca syndrome in primary and secondary SS was observed; namely, the reduction of myeloid DCs in blood was restored spontaneously with duration time of Sicca syndrome. We also examined the immunohistochemical staining of salivary glands of SS patients with monoclonal antibodies against fascin, CD11c and human leucocyte antigen DR (HLA-DR). Fascin + or CD11c + /HLA-DR + mononuclear cells were present in the salivary glands of secondary SS patients, as in primary SS. However, fascin + mononuclear cells were barely detected in the salivary glands of a chronic phase of SS patients. We also found a negative correlation between the frequency of blood myeloid DCs and salivary glandinfiltrating DCs in secondary SS patients, as well as primary SS. Our results suggest that the reduction of blood myeloid DCs and preferential trafficking of myeloid DCs into salivary glands is a common event in the early stage of SS. Myeloid DCs may play essential roles in the pathogenesis of Sicca syndrome of SS by initiating T helper cell immune responses.

Innate immunity in Sjögren's syndrome

“…Studies show DCs are decreased in peripheral blood and elevated in salivary tissue of pSS patients as compared to controls [19, 55, 56]. Evidence suggests that follicular DCs contribute to ectopic lymphoid neogenesis in salivary tissue in SS, as these cells promote expansion of T cells and are also associated with somatic hypermutation of B cells [57].…”

Circulating Myeloid Dendritic Cells is Decreased in the Acute Phase of Kawasaki Disease

“…This association between reduced number of circulating DCs and diseases activity is reported in many types of autoimmune diseases such as Sjögren's syndrome [11,12], systemic lupus erythematosis [13], sarcoidosis [14], and graft versus host disease [15]. In patients with graft-versus-host disease [15], the decrease in circulating DCs is associated with the clinical manifestations of disease in temporal profile.…”

“…When patients showed active skin or liver disease, the number of circulating DCs reduced. In these diseases, mature DCs were reported to be found in active lesion of the disease, such as in labial salivary glands in Sjögren syndrome [11,12], in granulomas together with T cells in sarcoidosis [14], and in skin biopsy specimen of graftversus-host disease [15]. In this study, the number of circulating DCs was associated with laboratory maker of disease severity of Kawasaki disease such as serum level of albumin; the characteristic change in KD [25,26] and levels of inflammatory pro-cytokines, CRP and IL-6.…”

“…However, it is possible that the reduced number of circulating DC could be due to their enhanced recirculation from blood to affected tissues. In Sjögren syndrome, a negative correlation was observed between the number of circulating mDCs and the frequency of tissue-infiltrated DCs [12]. Therefore, selective trafficking of DCs into target tissues and the resultant decrease of the circulating pool of DCs might be one of the mechanisms.…”

“…Immature DCs are activated after the capture of antigens in circulation or affected tissues, and then the activated DCs migrate through lymphatic vessels to lymphoid organs where they present processed antigens to naïve T cells [7][8][9][10]. Abnormalities of DC homeostasis have been involved in the pathophysiology of various human diseases, including autoimmune diseases [11][12][13][14][15], ischemic heart disease [16], and viral infection [17][18][19].…”