Review of Excessive Cytosolic DNA and Its Role in AIM2 and cGAS-STING Mediated Psoriasis Development.

IF 1.9 4区 医学 Q3 DERMATOLOGY Clinical, Cosmetic and Investigational Dermatology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI:10.2147/CCID.S476785
Tongtong Xu, Xiaojing Zhong, Nana Luo, Wenyi Ma, Pingsheng Hao
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Abstract

In psoriasis, keratinocytes are triggered by factors, such as infection or tissue damage, to release DNA, which thereby activates plasmacytoid dendritic cells and macrophages to induce inflammation, thickened epidermis, and parakeratosis. The recognition of double-stranded (ds)DNA facilitates the activation of cytoplasmic DNA sensors absent in melanoma 2 (AIM2) inflammasome assembly and cyclic guanosine monophosphate adenosine monophosphate (cGAMP) synthase (cGAS) - stimulator of interferon gene (STING) pathway, both of which play a pivotal role in mediating the inflammatory response and driving the progression of psoriasis. Additionally, secreted proinflammatory cytokines can stimulate further DNA release from keratinocytes. Notably, the activation of AIM2 and cGAS-STING signaling pathways also mediates programmed cell death, potentially enhancing DNA overproduction. As a result, excessive DNA can activate these pathways, amplifying persistent inflammatory responses that contribute to the maintenance of psoriasis. Several studies have validated that targeting DNA and its mediated activation of AIM2 and cGAS-STING offers promising therapeutic strategies for psoriasis. Here, we postulate a hypothesis that excessive cytosolic DNA can activate AIM2 and cGAS-STING, mediating inflammation and programmed cell death, ultimately fostering DNA accumulation and contributing to the development of psoriasis.

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细胞质 DNA 过多及其在 AIM2 和 cGAS-STING 介导的牛皮癣发展中的作用综述。
在牛皮癣中,角质细胞受感染或组织损伤等因素的触发释放 DNA,从而激活浆细胞树突状细胞和巨噬细胞,诱发炎症、表皮增厚和角化不全。对双链(ds)DNA 的识别有助于激活黑色素瘤中缺失的细胞质 DNA 传感器 2(AIM2)炎性体组装和环鸟苷酸单磷酸腺苷(cGAMP)合成酶(cGAS)--干扰素基因刺激器(STING)通路,这两种通路在介导炎症反应和推动银屑病进展方面都起着关键作用。此外,分泌的促炎细胞因子可刺激角质形成细胞进一步释放 DNA。值得注意的是,AIM2 和 cGAS-STING 信号通路的激活也会介导细胞的程序性死亡,从而可能促进 DNA 的过度产生。因此,过量的 DNA 会激活这些通路,扩大持续的炎症反应,从而导致银屑病的持续存在。一些研究已经证实,针对 DNA 及其介导的 AIM2 和 cGAS-STING 激活可为银屑病提供有前景的治疗策略。在此,我们提出一个假设,即细胞膜 DNA 过多可激活 AIM2 和 cGAS-STING,介导炎症和程序性细胞死亡,最终促进 DNA 积累并导致银屑病的发生。
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来源期刊
CiteScore
2.80
自引率
4.30%
发文量
353
审稿时长
16 weeks
期刊介绍: Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal. Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest. The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care. All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.
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