The numbers of Foxp3 + Treg cells are positively correlated with higher grade of infiltration at the salivary glands in primary Sjögren's syndrome

Abstract

This study was designed to investigate whether Foxp3( +) regulatory T (Treg) cells play a role in the histopathologic changes of primary Sjögren's Syndrome (pSS) and to evaluate other factors possibly associated with Foxp3(+) Treg cells in pSS patients. The number of FoxP3-expressing T cells in peripheral blood (PB) of 39 patients with pSS, 40 patients with rheumatoid arthritis (RA), and 28 healthy controls was measured by flow-cytometer analysis. FoxP3-expressing CD4(+)CD25(+) Treg cells were analyzed in minor salivary gland (SG) tissues of 39 pSS patients. Histopathologic changes were examined by light microscopy according to Chisholm's classification. Immunohistochemistry and immunofluorescence were performed to assess the Foxp3(+) Treg in SG biopsy specim-ens. The numbers of CD4(+) T cells and FoxP3-expressing CD4(+) T cells in PB were similar in all groups. Expression of CD25 on CD4(+) T cells in PB of patients with pSS and RA was significantly higher than in healthy controls, especially for RA patients. Immunohistochemistry and immunofluorescence showed that FoxP3(+) Treg were enriched in the SGs of pSS patients, with a positive correlation between the increase in FoxP3(+) Treg in SG and the Chisholm score in pSS (p < 0.001, r = +0.605). The increase of FoxP3( +) Treg cells in the SGs of pSS patients, which is correlated with gland infiltration, suggests that natural regulatory T cells play an important role in the pathogenesis of pSS. Further studies are required to explore the mechanisms that mediate the relationship between Treg and the pathogenesis of pSS.

Expansion of CD4+CD25-GITR+ regulatory T-cell subset in the peripheral blood of patients with primary Sjögren's syndrome: correlation with disease activity

“…Subsequent studies focused on evaluating the possible involvement of T REG in the human manifestations of these pathologies in order to identify phenotypic and/or functional alterations of these cells during the disease course. Data published on Sjögren's syndrome (SS), are all substantially in agreement that the percentages of peripheral blood of T REG cells, identified by high CD25 expression and/or expression of FoxP3, of affected patients are identical to or slightly lower than those of healthy controls (15)(16)(17)(18). Furthermore, extremely interesting results are emerging from immunohistochemical studies of the salivary glands in SS.…”

“…Furthermore, extremely interesting results are emerging from immunohistochemical studies of the salivary glands in SS. These show a correlation between the lymphocytic infiltrate of the salivary glan-original article Expansion of CD4+CD25-GITR+ regulatory T-cell subset in the peripheral blood of patients ds (evaluated both by the Chisholm score and by the focus score) and the number of T REG cells present in the saliva (16)(17)(18). In other words, even though the presence of a T REG cell population has been observed at the site of inflammation, these cells do not seem to be able to reduce the lymphocytic infiltrate or, consequently, the parenchymal damage caused by it.…”

FOXP3 Expression in Duodenal Mucosa in Pediatric Patients with Celiac Disease

“…The mechanisms regulating the increase in FOXP3 + Treg numbers in M2 and M3 stages of celiac disease, which are similar to those described by others for salivary gland tissue of primary Sjögren's syndrome [27] , are not fully understood. It is one possibility that there is a general increase in lymphocyte activation and expansion which is regulated by proinflammatory cytokines during advanced stages of celiac disease [28] .…”

Granulomatous Pigmented Purpuric Dermatitis Associated with Primary Sjögren’s Syndrome

“…Concerning Foxp3-i-Tregs in SS, several reports suggested that the numbers of Foxp3+ Tregs are positively correlated with SS (11,12). Sarigui et al (11) reported that Foxp3+ Tregs were enriched in the salivary glands and associated with the Chisholm score in primary SS.…”