Maehara T, Moriyama M, Hayashida JN, et al. Selective localization of T helper subsets in labial salivary glands from primary Sjögren's syndrome patients

Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka, Japan.
Clinical & Experimental Immunology (Impact Factor: 3.04). 08/2012; 169(2):89-99. DOI: 10.1111/j.1365-2249.2012.04606.x
Source: PubMed


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 (T(regs)) 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 T(regs) 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 T(reg)-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.

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Available from: Masafumi Moriyama, Feb 25, 2014
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    • "Furthermore, IL- 4 and IL-21 receptors knockout mice have greatly reduced IgG responses, indicating that IL-21 co-operates with IL-4 to regulate humoral immune responses [68]. We previously observed that Tfh-related molecules, CXCR5 and B-cell lymphoma 6 protein (Bcl-6), were highly expressed on infiltrating lymphocytes in ectopic GCs of LSG lesions from both SS and IgG4-DS patients [15] [36]. These results provide strong support for Tfh cells in the progression of disease as a lymphoproliferative disorder, particularly in the growth and activation of ectopic GC formation (Fig. 3). "
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