Localization of Th subsets in salivary glands of Sjögren’s syndrome

Objectives: Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into the salivary glands. Recently, T helper (Th) 17, regulatory T cells (Treg), and follicular helper T cells (Tfh) had been shown to have critical function in a variety of autoimmune disease, including Th1 and Th2. Moreover, the localization of these Th subsets at each part of lesion has been not still poorly understood. In this study, we thus investigated the localization of these Th subsets in the labial salivary glands (LSGs) from SS patients, using laser capture microdissection (LCM). Methods: The mRNA expression of cytokines and transcription factors associated with these Th subsets in the whole LSGs from 54 SS patients and 16 healthy controls was examined by real-time PCR. Additionally, infiltrating lymphocytes without germinal center (GC): (GC-) and with GC: (GC+) in the LSG specimens from 8 SS patients was extracted by LCM. The mRNA expression of these molecules was compared between each two groups by real-time PCR and immunostaining in order to assess the propagation of the disease process in the same SS patient. Results: The mRNA expression of cytokines and transcription factors of Th1, Th2, TH17, and Tfh in the LSGs from SS patients was significantly increased in comparison with that in the controls, while the mRNA expression of Th2 and Tfh was closely associated with strong lymphocytic accumulation. In the microdissected tissues, Th1 and Th17 type molecule were strongly detected in the GC-, while Th2 and Tfh type molecule were strongly detected in the GC+. In contrast, no significant difference was observed in Treg type molecule. Conclusions: These results suggest that SS had definitive localization of Th subsets in the lesions of LSGs and might be initiated by Th1 and Th17 cells and progressed in association with Th2 and Tfh cells.