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原发性干燥综合征中针对JAK/STAT通路的治疗

JAK/STAT Pathway Targeting in Primary Sjögren Syndrome.

作者信息

Gandolfo Saviana, Ciccia Francesco

机构信息

Rheumatology Unit, Department of Internal Medicine, San Giovanni Bosco Hospital, Naples, Italy.

Department of Precision Medicine, Università della Campania Luigi Vanvitelli, Naples, Italy.

出版信息

Rheumatol Immunol Res. 2022 Oct 20;3(3):95-102. doi: 10.2478/rir-2022-0017. eCollection 2022 Oct.

Abstract

Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease mainly affecting exocrine glands and resulting in disabling symptoms, as dry eye and dry mouth. Mechanisms underlying pSS pathogenesis are intricate, involving multiplanar and, at the same time, interlinked levels, e.g., genetic predisposition, epigenetic modifications and the dysregulation of both immune system and glandular-resident cellular pathways, mainly salivary gland epithelial cells. Unravelling the biological and molecular complexity of pSS is still a great challenge but much progress has been made in recent years in basic and translational research field, allowing the identification of potential novel targets for therapy development. Despite such promising novelties, however, none therapy has been specifically approved for pSS treatment until now. In recent years, growing evidence has supported the modulation of Janus kinases (JAK) - signal transducers and activators of transcription (STAT) pathways as treatment strategy immune mediated diseases. JAK-STAT pathway plays a crucial role in autoimmunity and systemic inflammation, being involved in signal pathways of many cytokines. This review aims to report the state-of-the-art about the role of JAK-STAT pathway in pSS, with particular focus on available research and clinical data regarding the use of JAK inhibitors in pSS.

摘要

原发性干燥综合征(pSS)是一种自身免疫性全身性疾病,主要影响外分泌腺,导致诸如干眼和口干等致残症状。pSS发病机制复杂,涉及多个层面且相互关联,例如遗传易感性、表观遗传修饰以及免疫系统和腺体内驻留细胞途径(主要是唾液腺上皮细胞)的失调。揭示pSS的生物学和分子复杂性仍然是一项巨大挑战,但近年来基础和转化研究领域已取得很大进展,使得能够确定潜在的新型治疗靶点。然而,尽管有这些有前景的新发现,但迄今为止尚无专门批准用于pSS治疗的疗法。近年来,越来越多的证据支持调节Janus激酶(JAK)-信号转导子和转录激活子(STAT)途径作为免疫介导疾病的治疗策略。JAK-STAT途径在自身免疫和全身炎症中起关键作用,参与多种细胞因子的信号通路。本综述旨在报告关于JAK-STAT途径在pSS中的作用的最新进展,特别关注有关在pSS中使用JAK抑制剂的现有研究和临床数据。

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