Session Title: Sjögren's Syndrome - Clinical
Session Type: Abstract Submissions (ACR)
Thymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory cytokine involved in Th2-mediated immune responses and homeostatic T-cell expansion. Reduced TSLP expression by intestinal epithelial cells was recently shown to lead to reduced Th2 responses and development of Th1-mediated experimental colitis. In addition, TSLP is described as a proinflammatory factor in rheumatoid arthritis, which is driven by Th1/Th17 responses. A Th1/Th17 polarized environment is also present in the salivary glands of patients with Primary Sjögren’s syndrome (pSS).The aim of this research was to investigate TSLP expression in salivary glands of pSS patients as compared to non-SS Sicca (nSS) patients and to study the relationship to local and systemic disease parameters.
Tissue sections of minor salivary glands from 38 pSS and 18 nSS patients were stained with a monoclonal antibody (mAb) against human TSLP or an isotype control. In addition, sections were stained with a mAb against the epithelial cell marker Cytokeratin High Molecular Weight (CK HMW) or stained with alcian blue to detect mucus production. The number of cells that stained positive for TSLP was assessed. In addition, TSLP was quantified at sites where only intact (CK HMW positive), functional (alcian blue positive) structures were present. TSLP expression was correlated to local (lymphocyte focus score, LFS; %IgA positive plasma cells) and systemic (erythrocyte sedimentation rate, ESR; serum IgG levels) disease parameters.
TSLP was almost exclusively expressed by acinar cells in both pSS and nSS patients. The number of TSLP-expressing cells per mm2 was significantly decreased in pSS patients as compared to nSS patients (462 ± 42 vs. 773 ± 84, p<0.01) and correlated negatively to LFS (r= -0.48, p<0.001) ESR (r= -0.41, p<0.01), serum IgG levels (r= -0.41, p<0.01) and positively to the percentage of local IgA producing plasma cells (r= 0.35, p<0.05). At sites with intact, functional epithelium TSLP expression tended to be reduced in pSS patients as compared to nSS patients (840 ± 75 vs. 1064 ± 72, p=0.079). Furthermore, pSS patients with a LFS equal to or higher than 3 had significantly lower numbers of TSLP-producing cells per mm2 at these sites compared to nSS patients (677 ± 105 vs. 1064 ± 72, p<0.01). Also, in intact and functional epithelium, the number of TSLP-producing cells correlated negatively to LFS (r= -0.40, p<0.01), ESR (r= -0.32, p<0.05) and serum IgG levels (r= -0.27, p<0.05)
TSLP expression is reduced in pSS patients, associated with local and systemic inflammatory markers including increased lymphocytic infiltration. Considering the described role of TSLP in promoting Th2 responses at mucosal sites, we hypothesize that TSLP is constitutively expressed in salivary glands and promotes a protective Th2 milieu, whereas loss of TSLP expression may contribute to Th1/Th17 associated immunopathology in pSS.
M. R. Hillen,
A. A. Kruize,
M. Wenting-van Wijk,
F. P. J. G. Lafeber,
C. E. Hack,
J. A. G. van Roon,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-expression-of-tslp-in-labial-salivary-glands-of-patients-with-pss-is-associated-with-local-and-systemic-disease-parameters/