Selective localization of T helper subsets in labial salivary glands from primary Sjögren's syndrome patients

Abstract

The aim of this study was to investigate the initiation and progression of autoimmune damage in the lesions of labial salivary glands (LSGs) from primary Sjögren's syndrome (SS) patients by examining the selective localization of T helper (Th) subsets such as Th1, Th2, Th17 regulatory T cells (Tregs) and follicular T helper cells (Tfh). The expression of cytokines and transcription factors associated with these Th subsets in the LSGs from 54 SS patients and 16 healthy controls was examined using real-time polymerase chain reaction (PCR) and immunostaining. Additionally, infiltrating lymphocytes without germinal centre (GC-) and with GC (GC+) in the LSGs specimens from eight SS patients were extracted selectively by laser capture microdissection (LCM). The mRNA expression of these molecules was compared between the two sample groups of GC- and GC+ by real-time PCR. The mRNA expression of cytokines and transcription factors of all T helper (Th) subsets in the LSGs from the SS patients was increased significantly in comparison with controls. In LSGs from the SS patients, Th2 and Tfh was associated closely with strong lymphocytic infiltration; however, Th1, Th17 and Tregs was not. In the selectively extracted lesions of LSGs, Th1 and Th17-related molecules were detected strongly in the GC-, while Th2 and Tfh-related molecules were detected in the GC+. In contrast, no significant association with strong lymphocytic infiltration was observed in Treg-related molecules. These results indicate that SS has selective localization of Th subsets such as Th1, Th2, Th17 and Tfh in the LSGs, which is associated closely with disease severity and/or status. SS might be initiated by Th1 and Th17 cells, and then progressed by Th2 and Tfh cells via GC formation.

Analysis of IL10 haplotypes in primary Sjögren’s syndrome patients from Western Mexico: Relationship with mRNA expression, IL-10 soluble levels, and autoantibodies

“…High IL10 expression levels were found in pSS patients in our study. Previous works showed high IL10 mRNA expression in salivary glands of pSS patients [49][50][51][52]. Furthermore, Fox et al suggested that salivary gland CD4+ T cells produce over 40-fold more IL10 mRNA than peripheral blood CD4+ T cells from the same patient or normal controls, moreover, increased levels of IL-10 were found in saliva of pSS patients suggesting that the elevated mRNA levels detected in their glandular tissue correlated with local protein synthesis [49].…”

A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjögren’s syndrome and systemic lupus erythematosus

“…Patients with higher Tfh cell proportions also had elevated serum levels of IL-12 and IL-21 [6]. Maehara et al have described that the expression of Th2 and certain Tfh-related molecules was associated with robust lymphocytic accumulation and ectopic GC formation [7]. We also investigated the localization of Tfh cells in the lymphocyte infiltration in labial salivary gland (LSG) biopsies gained from pSS patients at the time of disease onset, and found that Tfh cell markers [CD84, PD-1 and B cell lymphoma 6 protein (Bcl-6)] occurred predominantly in more organized lymphoid structures with higher focus scores [8], which indicates that Tfh cells may also be good therapeutic targets in pSS.…”

Salivary Gland Pathology in Sjögren's Syndrome

“…52 Nonetheless, significant increase in T H 2 cytokines is observed in GC-positive patients. 53 The authors' group previously demonstrated the association between IL-18, a known cytokine involved in the T H 1/T H 2 switch, with the increased production of antibodies against ENA. 54 Another cytokine, IL-21, involved in T H 17 cell homeostasis, plasma cells differentiation, and GC formation, is found in pSS salivary glands.…”