THU0241 Decreased circulating CXCR3+CCR9+ th cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with SJÖGREN'S syndrome to potentially facilitate concerted migration

Background Primary Sjogren9s syndrome (pSS) is characterized by dryness and lymphocytic infiltration in the salivary glands. Both CXCR5+ T follicular helper (Tfh) cells and CCR9+ Tfh-like cells and their specific chemotactic ligands CXCL13 and CCL25 are present at increased levels in the salivary glands of pSS patients. Recently, we and others found that CCR9+ Th cells are elevated in pSS peripheral blood and co-express CXCR3 and other chemokine receptors, known to be differentially expressed by Th cell subsets. CCR9+ Th cells play an important role in mucosal immunity and have been shown to produce high levels of IFN-γ, like CXCR3+ Th1 cells. Since ligands of CXCR3 (CXCL9/10/11) are abundantly expressed in the salivary glands of pSS patients the potential role of this receptor in conjunction with CCL25 was studied in comparison with other chemokine receptors. Objectives To study potential chemokine interactions causing enhanced migration of CCR9+ T cells into the salivary glands in pSS. Methods CXCL10, CCL25, CXCL13, CCL17 and CCL20 mRNA and protein expression in the salivary gland of pSS and non-Sjogren9s sicca (nSS) patients was assessed (mRNA: n=9 vs n=9 and protein: n=26 vs n=34, respectively). Frequencies of CXCR3, CCR9, CXCR5, CCR4 and CCR6 expressing Th cells in blood of pSS patients and healthy controls were assessed by flow cytometry (n=11 vs n=11). Chemotaxis assays (n=3 HC, n=5 pSS) were performed to study migration induced by CXCL10 and CCL25. Results CCL25, CXCL10 and CXCL13 expression were increased in pSS compared to nSS patients, both at mRNA and protein level (all p≤0.02). CCL17 and CCL20 expression were low and detectable in only few patients. Protein levels of CXCL10 and CXCL13 correlated with lymphocytic focus scores and all 3 chemokines correlated with serum IgG levels in pSS (all p Conclusions The decreased frequency of CXCR3+CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation. Elevated expression of ligands CXCL10 and CCL25 in the salivary gland and the synergistic effect on chemotaxis in vitro indicate a potential role for these chemokines in formation of lymphocytic infiltrates in exocrine glands of pSS patients. Disclosure of Interest None declared