Increased interleukin (IL)-7Rα expression in salivary glands of patients with primary Sjogren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity.
OBJECTIVE
To identify interleukin (IL)-7Rα expression in the labial salivary gland (LSG) of patients with primary Sjögren's syndrome (pSS) and non-Sjögren's syndrome sicca (nSS-sicca) and to study its correlation with glandular inflammation and IL-7 expression.


METHODS
The presence of infiltrating immune cells and IL-7Rα cells in inflamed LSG of patients with pSS (n=12) and nSS-sicca controls (n=7) was studied by immunohistochemistry and fluorescence activated cell sorting analysis upon tissue digestion (n=15 and n=13, respectively). Additionally, the correlations of IL-7Rα cells with hallmark disease parameters of pSS, major infiltrating inflammatory cells and IL-7 were assessed.


RESULTS
In the LSG of patients with pSS increased numbers of IL-7Rα cells were found as compared with nSS-sicca patients. IL7Rα cells strongly correlated with the lymphocytic focus score, IL-7 expression, the decrease in percentage of IgA plasma cells and numbers of CD3 T cells, CD20 B cells, and CD1a and CD208 myeloid dendritic cells. Analysis of isolated cells from the LSG demonstrated strongly increased percentages of IL-7Rα CD3 T cells in pSS as compared with nSS, showing abundant IL-7Rα expression on both CD4 and CD8 T cells. Other CD45 leucocytes and CD45- tissue cells scarcely expressed IL-7Rα. Percentages of IL-7Rα T cells also significantly correlated with glandular inflammation.


CONCLUSIONS
This study shows the presence of increased IL-7Rα T cells in the LSG of patients with pSS and their association with the severity of sialadenitis, disease parameters and IL-7 expression. Considering the immunostimulatory ability of IL-7Rα T cells and IL-7, this suggests that IL-7(R)-dependent T cell-driven immune activation plays an important role in inflammation in pSS.
UMC Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands.
A
A
Bikker
A A
AA
Kruize
M
M
Wenting
M A
MA
Versnel
J W J
JW
Bijlsma
F P J G
FP
Lafeber
J A G
JA
van Roon
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020395:Receptors, Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012793:Sialadenitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; C508605:IL7 protein, human; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain