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IL-7 receptor effector T cells are increased in the inflamed salivary glands of pSS patients and correlate with inflammatory markers
  1. A Bikker1,
  2. AA Kruize1,
  3. M Wenting1,
  4. M Versnel2,
  5. JWJ Bijlsma1,
  6. FPJG Lafeber1,
  7. JAG van Roon1
  1. 1Department of Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
  2. 2Department of Immunology, Erasmus MC Rotterdam, Rotterdam, The Netherlands

Abstract

In patients with pSS local T cell-driven inflammation contributes to destruction of exocrine glands associated with clinical symptoms of dryness. Recently the authors documented increased interleukin (IL)-7 in labial salivary glands (LSG) of pSS patients that was capable to induce Th1 and Th17 activity and proinflammatory cytokine secretion. IL-7 mediates its effects by signaling through the high affinity IL-7Rα subunit and γc chain. The authors and others have shown that IL-7R+ CD4 T cells that strongly proliferate upon TCR activation, while IL-7R CD4 T cells are anergic and can be regulatory of nature. This suggests that IL-7R+ T cells contribute to the increased inflammatory response in LSG of pSS patients, especially in the presence of increased local IL-7 expression.

To identify IL-7R expression in the labial salivary gland and to examine the phenotypical characteristics of IL-7R+ T cells between pSS and non-Sjögren's syndrome sicca (nSS) patients. The presence of infiltrating immune cells and IL-7R+ cells in inflamed salivary glands of pSS patients (n=14) and non-inflamed LSG of nSS patients (n=7) was studied by immunohistochemistry and FACS analysis upon tissue digestion.

In the LSG of pSS patients significantly increased numbers of IL-7R+ cells were found as compared to nSS (pSS vs nSS; 244.3±40.7 vs 12.3±4.6 cells/mm2). IL7R+ T cells were found throughout the tissue but mainly in the CD3-rich lymphocytic areas. IL7R+ T cells significantly (all p<0.01) correlated with local disease parameters (lymphocytic focus score (LFS); r=0.744 and % IgA+ cells r=−0.658) as well as with immune cells present in the LSG (CD3 r=0.890; CD20 r=0.717; CD1a r=0.660; CD208 r=0.763).

FACS analysis of isolated cells from patients' LSG confirmed a strongly increased percentage of both CD3 and IL-7R+ CD3 T cells in pSS as compared to nSS (both p<0.01). Furthermore, abundant IL-7R expression was detected on high proportions of CD4 and CD8 (on average 66% ± 5% and 56% ± 4%, respectively). Other CD45+ leucocytes and CD45 tissue cells did not or hardly express the IL-7R. IL-7R+ CD3, CD4 and CD8 T cells as percentage of the total LSG cells significantly correlated with the LFS (p≤0.05, r=0.533; p≤0.01, r=0.593; p≤0.01, r=0.631, respectively).

The abundant presence of IL-7R+ T cells in the inflamed salivary glands of pSS patients, which correlates to inflammation, suggests that increased IL-7 expression could significantly contribute to glandular inflammation by activation of IL-7R+ effector T cells. Hence, blockade of the IL-7R might be a novel therapeutic strategy for pSS.

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