IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome

Hwang, Sung Yeoun; Woo, Jin Seok; Moon, Jeonghyeon; Yang, SeungCheon; Park, Jin‐Sil; Lee, Jae‐Seon; Choi, Jung-Hwa; Lee, Kun Hee; Kwok, Seung‐Ki; Park, Sung-Hwan; Cho, Mi‐La

doi:10.3389/fimmu.2021.721453

Cited by 16 publications

(10 citation statements)

References 49 publications

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“…However, one study found no such difference ( 11 ). The increased Th17 cell frequency was also noted in the peripheral blood, spleen, and salivary glands of NOD mice ( 29 ).…”

Section: Role Of Cd4 + T Cells In Ssmentioning

confidence: 89%

Exploiting the role of T cells in the pathogenesis of Sjögren’s syndrome for therapeutic treatment

Zhao

Zhu

et al. 2022

Front. Immunol.

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Sjögrens syndrome (SS) is caused by autoantibodies that attack proprioceptive salivary and lacrimal gland tissues. Damage to the glands leads to dry mouth and eyes and affects multiple systems and organs. In severe cases, SS is life-threatening because it can lead to interstitial lung disease, renal insufficiency, and lymphoma. Histological examination of the labial minor salivary glands of patients with SS reveals focal lymphocyte aggregation of T and B cells. More studies have been conducted on the role of B cells in the pathogenesis of SS, whereas the role of T cells has only recently attracted the attention of researchers. This review focusses on the role of various populations of T cells in the pathogenesis of SS and the progress made in research to therapeutically targeting T cells for the treatment of patients with SS.

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“…However, one study found no such difference ( 11 ). The increased Th17 cell frequency was also noted in the peripheral blood, spleen, and salivary glands of NOD mice ( 29 ).…”

Section: Role Of Cd4 + T Cells In Ssmentioning

confidence: 89%

Exploiting the role of T cells in the pathogenesis of Sjögren’s syndrome for therapeutic treatment

Zhao

Zhu

et al. 2022

Front. Immunol.

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“…[45][46][47] Indeed, IL-17 has been shown to impair salivary gland function by affecting calcium movement. [48] It has been linked to promoting salivary gland inflammation and cell death in conditions like SS, [49] which can activate nuclear factor κB. This transcription factor plays a leading role in regulating the expression of various proinflammatory cytokines (TNF-α, IL-1β, IL-6, and C-C motif chemokine ligand 2).…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren’s syndrome

Hong,

Chen,

Ren

et al. 2023

Medicine

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This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren’s syndrome (SS) by combining network pharmacology with molecular docking techniques. YP’s active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP’s capacity to reduce TNF-α, IL-1β, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1β), providing experimental evidence for its clinical application in treating SS.

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“…It was subsequently found that the aberrant expression of IL-17 induced by metabolic abnormalities contributed to cell lesions and inhibition of tissue recovery in the salivary glands of patients with SS. Furthermore, retinoic A deficiency can exacerbate the imbalance in the Th17/Treg ratio in patients with SS ( 69 ).…”

Section: Pathogenesismentioning

confidence: 99%

Pathogenesis and treatment of Sjogren’s syndrome: Review and update

et al. 2023

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Sjogren’s syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, and lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 and IL-23), and B cell-related cytokines (TNF and BAFF) are crucial for the pathogenesis of SS. We also summarize the advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, targeting BAFF, inhibiting JAK pathway, et al. Similar to that of SLE, RA, and MS, biotherapeutic strategies of SS consist of neutralizing antibodies and inflammation-related receptor blockers targeting proinflammatory signaling pathways. However, clinical research on SS therapy is comparatively rare. Moreover, the differences in the curative effects of immunotherapies among SS and other autoimmune diseases are not fully understood. We emphasize that targeted drugs, low-side-effect drugs, and combination therapies should be the focus of future research.

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IL-17 and CCR9+α4β7– Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren’s Syndrome

Cited by 16 publications

References 49 publications

Exploiting the role of T cells in the pathogenesis of Sjögren’s syndrome for therapeutic treatment

Exploiting the role of T cells in the pathogenesis of Sjögren’s syndrome for therapeutic treatment

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren’s syndrome

Pathogenesis and treatment of Sjogren’s syndrome: Review and update

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