Tofacitinib alleviated salivary gland inflammation and reduced the percentages of effector T cells in murine Sjögren's disease.

IF 3.4 4区医学 Q2 RHEUMATOLOGY

Clinical and experimental rheumatology Pub Date : 2024-10-29 DOI:10.55563/clinexprheumatol/b91fx8

Qinghong Liu, Xiaoyan Xing, Jing He

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引用次数: 0

Abstract

Objectives: The Janus kinases-signal transducer and activator of transcription (JAK-STAT) signalling pathway plays a crucial role in autoimmunity and the signalling pathways of many cytokines in Sjögren's disease (SjD). Therefore, the aim of this study was to investigate both the therapeutic and immunomodulatory effects of the oral JAK3/JAK2/JAK1 inhibitor tofacitinib in a murine model of SjD.

Methods: Tofacitinib or vehicle was administered orally to the mice with SjD for 6 weeks. Salivary flow rate was measured every three weeks. Pathological changes of salivary gland were detected by haematoxylin-eosin staining, and the percentages of subsets of CD4+ T cells and B cells in the cervical lymph nodes (cLNs) and spleen was determined by flow cytometry.

Results: Tofacitinib significantly ameliorated submandibular gland inflammation compared to the control group, as evidenced by reduced lymphocytic infiltration. Salivary flow rates improved significantly in tofacitinib treated mice compared to controls, indicating restored salivary gland function. The treatment also led to a substantial decrease in follicular helper T (Tfh) cells and the Tfh/Treg ratio in both the spleen and cLNs. Additionally, the frequencies of T helper 1 (Th1) and T helper 17 (Th17) cells were reduced in the spleen and cLNs.

Conclusions: Our data indicated that tofacitinib reduced percentages of effector T cells in an animal model of SjD. In addition, tofacitinib alleviated salivary gland inflammation and hypofunction, offering new insights into the clinical management of SjD.

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托法替尼缓解了唾液腺炎症，降低了小鼠斯约格伦病效应T细胞的百分比。

目的：Janus 激酶-信号转导和转录激活因子（JAK-STAT）信号通路在自身免疫和许多细胞因子信号通路在斯约戈伦病（SjD）中起着至关重要的作用。因此，本研究旨在探讨口服 JAK3/JAK2/JAK1 抑制剂托法替尼对小鼠 SjD 模型的治疗和免疫调节作用：给SjD小鼠口服托法替尼或药物6周。每三周测量一次唾液流量。结果：托法替尼能显著改善SjD小鼠颈淋巴结（cLNs）和脾脏中CD4+ T细胞和B细胞亚群的数量：结果：与对照组相比，托法替尼明显改善了颌下腺炎症，淋巴细胞浸润减少就是证明。与对照组相比，托法替尼治疗组小鼠的唾液流速明显提高，表明唾液腺功能得到恢复。治疗还导致脾脏和cLN中的滤泡辅助T（Tfh）细胞和Tfh/Treg比率大幅下降。此外，脾脏和 cLN 中的 T 辅助细胞 1（Th1）和 T 辅助细胞 17（Th17）的频率也降低了：我们的数据表明，托法替尼降低了SjD动物模型中效应T细胞的百分比。此外，托法替尼还能缓解唾液腺炎症和功能低下，为SjD的临床治疗提供了新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and experimental rheumatology 医学-风湿病学

CiteScore

6.10

自引率

18.90%

发文量

377

审稿时长

3-6 weeks

期刊介绍： Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.