JAK/STAT通路在原发性Sjögren综合征中的靶向作用

Saviana Gandolfo, Francesco Ciccia
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引用次数: 6

摘要

原发性Sjögren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,导致致残症状,如干眼和口干。pSS发病机制错综复杂,涉及多层面,同时也涉及相互关联的水平,例如遗传易感性、表观遗传修饰以及免疫系统和腺驻留细胞通路(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个巨大的挑战,但近年来在基础和转化研究领域取得了很大进展,从而可以识别潜在的新靶点,用于治疗开发。然而,尽管有这些有希望的新疗法,迄今为止还没有一种疗法被专门批准用于治疗pSS。近年来,越来越多的证据支持调节Janus激酶(JAK) -信号转导和转录激活因子(STAT)途径作为免疫介导疾病的治疗策略。JAK-STAT通路参与多种细胞因子的信号通路,在自身免疫和全身性炎症中起重要作用。本综述旨在报道JAK- stat通路在pSS中作用的最新进展,特别关注关于JAK抑制剂在pSS中使用的现有研究和临床数据。
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JAK/STAT Pathway Targeting in Primary Sjögren Syndrome.

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.

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