Treating Autoimmune Diseases With LANCL2 Therapeutics: A Novel Immunoregulatory Mechanism for Patients With Ulcerative Colitis and Crohn's Disease.

IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Inflammatory Bowel Diseases Pub Date : 2024-04-03 DOI:10.1093/ibd/izad258
Nuria Tubau-Juni, Raquel Hontecillas, Andrew J Leber, Sameeksha S Alva, Josep Bassaganya-Riera
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Abstract

Lanthionine synthetase C-like 2 (LANCL2) therapeutics have gained increasing recognition as a novel treatment modality for a wide range of autoimmune diseases. Genetic ablation of LANCL2 in mice results in severe inflammatory phenotypes in inflammatory bowel disease (IBD) and lupus. Pharmacological activation of LANCL2 provides therapeutic efficacy in mouse models of intestinal inflammation, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and psoriasis. Mechanistically, LANCL2 activation enhances regulatory CD4 + T cell (Treg) responses and downregulates effector responses in the gut. The stability and suppressive capacities of Treg cells are enhanced by LANCL2 activation through engagement of immunoregulatory mechanisms that favor mitochondrial metabolism and amplify IL-2/CD25 signaling. Omilancor, the most advanced LANCL2 immunoregulatory therapeutic in late-stage clinical development, is a phase 3 ready, first-in-class, gut-restricted, oral, once-daily, small-molecule therapeutic in clinical development for the treatment of UC and CD. In this review, we discuss this novel mechanism of mucosal immunoregulation and how LANCL2-targeting therapeutics could help address the unmet clinical needs of patients with autoimmune diseases, starting with IBD.

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LANCL2治疗自身免疫性疾病:溃疡性结肠炎和克罗恩病患者的一种新的免疫调节机制。
Lanthionine合成酶C样2(LANCL2)疗法作为一种新型的自身免疫性疾病治疗方式,已获得越来越多的认可。小鼠LANCL2的基因消融导致炎症性肠病(IBD)和狼疮的严重炎症表型。LANCL2的药理学激活在肠道炎症、系统性红斑狼疮、类风湿性关节炎、多发性硬化症和银屑病的小鼠模型中提供治疗功效。从机制上讲,LANCL2激活增强调节性CD4 + T细胞(Treg)反应和下调肠道中的效应器反应。通过参与有利于线粒体代谢和扩增IL-2/CD25信号传导的免疫调节机制,LANCL2激活增强了Treg细胞的稳定性和抑制能力。奥密克戎是晚期临床开发中最先进的LANCL2免疫调节治疗药物,是一种3期准备好的、一流的、肠道受限的、口服的、每天一次的小分子治疗药物,用于UC和CD的临床开发。在这篇综述中,我们讨论了粘膜免疫调节的这种新机制,以及LANCL2靶向疗法如何帮助解决自身免疫性疾病患者(从IBD开始)未满足的临床需求。
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来源期刊
Inflammatory Bowel Diseases
Inflammatory Bowel Diseases 医学-胃肠肝病学
CiteScore
9.70
自引率
6.10%
发文量
462
审稿时长
1 months
期刊介绍: Inflammatory Bowel Diseases® supports the mission of the Crohn''s & Colitis Foundation by bringing the most impactful and cutting edge clinical topics and research findings related to inflammatory bowel diseases to clinicians and researchers working in IBD and related fields. The Journal is committed to publishing on innovative topics that influence the future of clinical care, treatment, and research.
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