Objective. To study the expression levels and immunostimulatory capacities of interleukin-7 (IL-7) in primary Sjögren's syndrome.Methods. Labial salivary gland (LSG) IL-7 expression was determined by immunohistochemistry, using a quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with primary Sjögren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The correlation of IL-7 expression in LSGs with parameters of local and peripheral disease was studied, and serum and salivary IL-7 levels were determined. Additionally, the effects of IL-7 on cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with primary SS were determined in vitro by Luminex multicytokine assay and compared with the effects in control subjects.Results. The expression of IL-7 in LSGs was higher in patients with primary SS compared with that in patients with non-SS sicca syndrome. IL-7 was observed primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in patients with primary SS were higher than those in control subjects. In all 30 patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters of both local and peripheral disease. Furthermore, IL-7 stimulated T cell-attracting and T cell-differentiating cytokines (monokine induced by interferon-␥ [IFN␥], IFN␥-inducible 10-kd protein,

Objective. To evaluate the expression and functional ability of the high-affinity interleukin-7 receptor (IL-7R␣) in patients with rheumatoid arthritis (RA).Methods. Expression of IL-7R␣ and IL-7 was determined in synovial tissue from RA patients and was compared with that in synovial tissue from patients with undifferentiated arthritis (UA) and osteoarthritis (OA).

The present data suggest that IL7 is an important inducer of T cell-dependent TNFalpha production in RA joints. This may contribute to the correlation of intra-articular IL7 and TNFalpha in these joints. Furthermore, the persistence of IL7-induced inflammatory activity on TNFalpha blockade in vitro and persistence of IL7 levels and disease activity in anti-TNFalpha non-responders suggest that IL7 might additionally promote TNFalpha-independent inflammation.

Reduced TSLP expression in pSS patients is associated with increased local and systemic inflammatory markers. Loss of TSLP expression may contribute to Th1/Th17-associated immunopathology in pSS, in line with previous studies demonstrating that TSLP promotes a protective Th2 milieu at mucosal sites.

Background In patients with primary Sjögren’s syndrome (pSS), local T and B cell-driven inflammation contributes to destruction of exocrine glands associated with clinical symptoms of dryness. Recently increased IL-7 and IL7R expression in labial salivary glands (LSG) of pSS patients was documented. IL-7 causes T cell-dependent monocyte activation. Although there are indications that IL-7 affects the activity of developing human B-cells, the effect of IL-7 on mature B cell activation in human autoimmune diseases has not been reported previously. Because B cell activation plays a pivotal role in pSS pathology we investigated the capacity of IL-7 to induce (T cell-dependent) B-cell activation. Objectives To study the association of proliferating cells and interleukin-7 (IL-7) in the labial salivary gland (LSG) of pSS and non-Sjögren’s syndrome sicca (nSS-sicca) patients and the role of IL-7 in vitro to induce (T cell-dependent) B cell activation in vitro. Methods LSG from pSS and nSS-sicca patients were stained for Ki67 and correlated to the expression of IL-7. Peripheral blood mononuclear cells (PBMCs) and isolated CD4 T and B cells were analysed for ex vivo expression of the IL-7Rα. Analysis of activation markers (CD25, CD69 and HLA-DR) on CD4 T cells and B cells and proliferation of lymphocytes were determined after culture with IL-7 (3H-thymidine incorporation and Ki67 expression). Results An increased number of Ki67-proliferating cells per mm2 was found in the LSG of pSS as compared to nSS patients (pSS vs. nSS; 141±24 vs. 49±4, p<0.001), mainly confined to lymphocytic infiltrates. The number of these proliferating cells significantly correlated to the expression of IL-7 in LSG (r=0.643, p<0.001). In contrast to abundant IL-7R expression on CD4 T cells, CD19 B cells did not express IL-7Rα on their surface. In line with this IL-7 did not activate B cells directly, however in PBMC and CD4/CD19 co-cultures IL-7 significantly increased proliferation of and activation markers on both CD4 T cells (Ki67+ cells from 1.1±0.2% to 14.4±3.7%, p<0.01; CD25+ cells from 28.8±4.0% to 79.8±2.4%, p≤0.001; HLA-DR+ cells from 6.3±0.9% to 7.8±1.2%, p<0.05), and CD19 B cells (KI67+ cells from 1.9±0.3% to 4.1±0.9%, p<0.05; HLA-DR MFI from 282±110 to 375±135, p<0.05; mean increase of 37%). Conclusions To our knowledge, this is the first time that IL-7-induced T cell-dependent activation of mature B cells, which lack membrane expression of IL-7Rα, is demonstrated in humans. Together with the strong association of increased IL-7 expression and proliferating cells in the LSG of pSS, these results suggest that IL-7 is an important mediator in the immunopathology of pSS through activation of both T and indirectly B cells. Disclosure of Interest None Declared