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从实验室到临床:靶向白细胞介素-22信号通路治疗特应性皮炎的潜力

From Bench to Clinic: the Potential of Therapeutic Targeting of the IL-22 Signaling Pathway in Atopic Dermatitis.

作者信息

Jin Mirim, Yoon Juhan

机构信息

Department of Microbiology, College of Medicine, Gachon University, Incheon 21999, Korea.

Department of Health Science and Technology, Gachon Advanced Institute for Health Sciences & Technology (GAIHST), Gachon University, Incheon 21999, Korea.

出版信息

Immune Netw. 2018 Dec 19;18(6):e42. doi: 10.4110/in.2018.18.e42. eCollection 2018 Dec.

Abstract

Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD. Moreover, we also experimentally proved that IL-22 contributes to the pathophysiology of AD by employing a murine model of AD induced by epicutaneous sensitization. Here, we review recent preclinical and clinical findings that have advanced our understanding of the roles of IL-22 and Th22 cells in skin inflammation. We conclude that blockade of IL-22 signaling may be a promising therapeutic approach for the treatment of AD.

摘要

特应性皮炎(AD)是最常见的瘙痒性炎症性皮肤病,其特征为表皮和真皮增厚以及多种致病性极化T淋巴细胞浸润,包括Th2、Th17和Th22细胞。在开发治疗AD的靶向疗法方面已取得重大进展,例如美国食品药品监督管理局批准的度普利尤单抗,一种双靶向IL-4和IL-13信号通路的抗体。此外,越来越多已发表的证据以及抗IL-22抗体ILV-094临床试验早期阶段的有前景结果,有力地支持了IL-22是治疗AD的潜在治疗靶点这一观点。此外,我们还通过采用经皮致敏诱导的AD小鼠模型,实验证明了IL-22参与AD的病理生理学过程。在此,我们综述了最近的临床前和临床研究结果,这些结果加深了我们对IL-22和Th22细胞在皮肤炎症中作用的理解。我们得出结论,阻断IL-22信号通路可能是治疗AD的一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a160/6312894/2aa659ff10b3/in-18-e42-g001.jpg

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