Immunobiology of T Cells in Sjögren’s Syndrome

Yao, Yuan; Jin, Fang; Chang, Christopher; Xu, Ting; Gao, Cai; Gershwin, M. Eric; Lian, Zhe Xiong

doi:10.1007/s12016-020-08793-7

Cited by 62 publications

(65 citation statements)

References 220 publications

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“…TGF-β-mediated Th17 cell differentiation is tightly coordinated with other multiple cytokines and is activated under certain conditions, such as the presence of T cell-made TGF-β1 [134,139,140]. The pathogenesis of SS is suspected as loss of immune tolerance and increased inflammatory factors, but the details require further research [141]. Whether TGF-β has a protective effect or pathogenic drive in SS needs in-depth investigations considering the content-dependent pleiotropic ability of TGF-β during immune regulation.…”

Section: Sjögren's Syndromementioning

confidence: 99%

TGF-β Pathway in Salivary Gland Fibrosis

Zhang

Yun

Han

et al. 2020

IJMS

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Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren’s syndrome. Potential therapeutic strategies that target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.

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Section: Sjögren's Syndromementioning

confidence: 99%

TGF-β Pathway in Salivary Gland Fibrosis

Zhang

Yun

Han

et al. 2020

IJMS

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“…The role of Tregs is uncertain because of a balance in between Tregs and Th17 cells [ 162 ]. Further soluble mediators, such as TGF-β, the level of which is increased in SGs of SS patients compared to controls, is required for both Treg and Th17 cell development [ 163 , 164 ].…”

Section: Adaptive Immune Cellsmentioning

confidence: 99%

Contributions of Major Cell Populations to Sjögren’s Syndrome

Witas

Gupta

Nguyen

2020

JCM

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Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The etiology of SS remains poorly understood, yet progress has been made in identifying progressive stages of disease using preclinical mouse models. The roles played by immune cell subtypes within these stages of disease are becoming increasingly well understood, though significant gaps in knowledge still remain. There is evidence for distinct involvement from both innate and adaptive immune cells, where cells of the innate immune system establish a proinflammatory environment characterized by a type I interferon (IFN) signature that facilitates propagation of the disease by further activating T and B cell subsets to generate autoantibodies and participate in glandular destruction. This review will discuss the evidence for participation in disease pathogenesis by various classes of immune cells and glandular epithelial cells based upon data from both preclinical mouse models and human patients. Further examination of the contributions of glandular and immune cell subtypes to SS will be necessary to identify additional therapeutic targets that may lead to better management of the disease.

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“…T cells are known to play an important role in SS [39]. Our previous study pointed out that SS-1 inhibits Th1 (CD4+ IFN-γ+ and CD4+ TNF-α+ cells) and Th2 (CD4+ IL-4+ c cells) polarization of mouse spleen cells and T cell proliferation in Sjögren's syndrome [9].…”

Section: Discussionmentioning

confidence: 98%

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

Lin

Panny

et al. 2021

Life

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Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

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Immunobiology of T Cells in Sjögren’s Syndrome

Cited by 62 publications

References 220 publications

TGF-β Pathway in Salivary Gland Fibrosis

TGF-β Pathway in Salivary Gland Fibrosis

Contributions of Major Cell Populations to Sjögren’s Syndrome

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

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