Review
Cell Biology
Zheng Wang, Xinli Hu, Peng Cui, Chao Kong, Xiaolong Chen, Wei Wang, Shibao Lu
Summary: This review provides a comprehensive summary of recent advances in our understanding of the role of the cGAS-STING pathway in modulating the inflammatory response in intervertebral disc degeneration (IVDD). It explores the connection between the cGAS-STING axis and apoptosis, autophagy, and pyroptosis in IVDD. Additionally, the therapeutic potential of targeting the cGAS-STING signaling pathway in IVDD treatment is discussed.
CELL DEATH DISCOVERY
(2023)
Article
Immunology
Zhi Huan Chew, Jianzhou Cui, Karishma Sachaphibulkij, Isabelle Tan, Shreya Kar, Kai Kiat Koh, Kritika Singh, Hong Meng Lim, Soo Chin Lee, Alan Prem Kumar, Stephan Gasser, Lina H. K. Lim
Summary: Intracellular recognition of tumor-derived nucleic acids can activate macrophages, leading to inflammasome activation in the tumor microenvironment, which initiates pro-inflammatory and anti-tumorigenic responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Ophthalmology
Menglu Yang, Vanessa Delcroix, Anton Lennikov, Nicholas Wang, Helen P. Makarenkova, Darlene A. Dartt
Summary: The study aimed to determine the pro-inflammatory effect of self-genomic DNA on myoepithelial cells (MECs) in the pathogenesis of primary Sjogren's syndrome (pSS). The results showed that self-gDNA activated AIM2 inflammasome and STING in MECs, leading to the secretion of pro-inflammatory cytokines, providing potential insights into the development of pSS.
Article
Multidisciplinary Sciences
Dong Wang, Junwei Zou, Jun Dai, Zhengwu Cheng
Summary: The study revealed that AIM2 expression was significantly down-regulated in gastric cancer tissues, associated with tumor size, lymph node metastasis, tumor staging, and poor prognosis in patients. Knockdown of AIM2 promoted cellular proliferation and migration, while overexpression had the opposite effect. Mechanistically, AIM2 was found to regulate the AKT signaling pathway, indicating a potential new target for gastric cancer treatment.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Sennan Zhu, Qiuyu Chen, Jindan Sun, Wenzhuo Du, Ziqi Chen, Mengqi Yu, Jiayu Tao, Yi Zhou, Yu Zhao, Qiong Zhang
Summary: This study investigated the roles of the cGAS-STING signal pathway and autophagy in endometriosis progression and explored the regulatory mechanism of the cGAS-STING signal pathway on autophagy. The expression levels of the cGAS-STING signal pathway and autophagy were increased in endometriosis. Overexpression of STING promoted autophagy and increased migration and invasion of endometrial stromal cells, while the addition of autophagy antagonists reversed these effects. STING antagonists inhibited autophagy in vivo and reduced the volume of ectopic lesions. These findings suggest that the cGAS-STING signal pathway promotes endometriosis development by upregulating autophagy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Xinyu Xu, Huanhuan Fan, Ying Yang, Shankun Yao, Wenhao Yu, Zijian Guo, Weihong Tan
Summary: By self-assembling virus-like particles with long DNA building blocks generated through rolling-circle amplification and covered with cationic liposomes, cGAS liquid phase condensation and STING signaling activation can be efficiently induced, leading to the production of inflammatory cytokines and boosting antitumor immunity. Additionally, these virus-like particles can also trigger the formation of AIM2 inflammasome and induce gasdermin D-mediated pyroptosis, further enhancing antitumor immunity. Thus, this study provides a simple and robust strategy for cancer immunotherapy for clinical application.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Medicine, Research & Experimental
Yunhai Luo, Daofeng Zheng, Tong Mou, Junliang Pu, Zuotian Huang, Wei Chen, Yuke Zhang, Zhongjun Wu
Summary: CMPK2 plays a crucial role in hepatic ischemia/reperfusion injury by regulating the NLRP3 pathway and liver function. The study demonstrates that CMPK2 is essential for NLRP3 inflammasome activation, highlighting it as an effective target to alleviate liver damage from I/R.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Biology
Maria Krivega, Clara M. Stiefel, Sahar Karbassi, Line L. Andersen, Narendra K. Chunduri, Neysan Donnelly, Andreas Pichlmair, Zuzana Storchova
Summary: Even a single chromosome gain can cause significant changes in human cell physiology, including alterations in DNA replication, autophagy, lysosomal degradation, and interferon response. The constitutive nuclear localization of TFEB in trisomic cells is characteristic and relies on cGAS-STING activation. The cGAS-STING pathway is identified as a key regulator responsible for activating autophagy and inflammatory response in human cells with extra chromosomes.
COMMUNICATIONS BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Suyavaran Arumugam, Binghua Li, Sri Lakshmi Tejaswi Boodapati, Michael H. Nathanson, Beicheng Sun, Xinshou Ouyang, Wajahat Z. Mehal
Summary: TGF-beta induces HSC transdifferentiation by releasing mitochondrial DNA and activating the cGAS-STING-IRF3 pathway.
Review
Virology
Hannah L. Wallace, Rodney S. Russell
Summary: It is well-known that viruses can activate various inflammasomes, leading to programmed cell death and release of inflammatory cytokines. Traditionally, RNA viruses were thought to activate NLRP3 inflammasomes, while DNA viruses activate AIM2 inflammasomes. However, recent research suggests that viruses can activate multiple inflammasome sensors simultaneously.
Article
Cell Biology
Lu Zhou, Yi-Fei Zhang, Fu-Hua Yang, Han-Qing Mao, Zhi Chen, Lu Zhang
Summary: This study identified the role of mtDNA as an inflammatory driver in odontoblasts, which defended against bacterial invasion through the cGAS-STING pathway. The findings suggest that targeting the mtDNA-cGAS-STING axis could be a potential therapeutic strategy for preventing severe bacterial inflammation in pulpitis.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Immunology
Ping Yi, Pengpeng Cao, Ming Yang, Feng Xiong, Jiao Jiang, Yang Mei, Yue Xin, Mingming Zhao, Haijing Wu, Qianjin Lu
Summary: In this study, it was found that CD44 expression was upregulated in B cells of SLE patients and MRL/lpr mice, accompanied by elevated AIM2 expression. Moreover, the ligand HA was abnormally increased in the serum of SLE patients. Further experiments revealed that the HA-CD44 interaction stimulated B-cell activation and upregulated the expression of AIM2 and the transcription factor STAT3. Blocking CD44 or suppressing the activity of STAT3 could inhibit B-cell activation and proliferation. These findings provide potential targets for SLE therapy.
CLINICAL IMMUNOLOGY
(2023)
Review
Genetics & Heredity
Jieyi Wang, Jing Gao, Cong Huang, Sohyun Jeong, Randy Ko, Xue Shen, Chaofeng Chen, Weilong Zhong, Yanfen Zou, Bo Yu, Changbing Shen
Summary: Research has revealed genetic and epigenetic associations between the AIM2 gene and psoriasis, while the formation and activation of the AIM2 inflammasome play a crucial role in the pathogenesis of psoriasis, suggesting that inhibiting the AIM2 inflammasome could be a novel therapeutic target for psoriasis.
FRONTIERS IN GENETICS
(2022)
Review
Immunology
Arun K. Mankan, Paulina Czajka-Francuz, Maria Prendes, Sriram Ramanan, Marcin Koziej, Laura Vidal, Kamal S. Saini
Summary: As the first responders, neutrophils lead the innate immune response by employing strategies such as phagocytosis, microbicide granules, ROS production, and NETs secretion. More recently, their ability to sense and respond to pathogen-associated molecular patterns is being recognized. This review summarizes current information about intracellular DNA recognition by neutrophils and proposes models of signal amplification in immune response. The clinical relevance of DNA sensing by neutrophils in infectious and non-infectious diseases including malignancy is also discussed.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Shiyuan Feng, Yongjun Yang, Zhenzhen Liu, Wei Chen, Chongtao Du, Guiqiu Hu, Shuixing Yu, Peixuan Song, Jinfeng Miao
Summary: Staphylococcus aureus can survive within phagocytes, and bacteriolysis is an early event during S. aureus infection that induces cell death. The cell death is AIM2-mediated necroptosis rather than apoptosis or pyroptosis. Gene expression associated with apoptosis is inhibited during S. aureus infection. Increased bacteriolysis enhances S. aureus pathogenicity and triggers inflammatory response mediated by AIM2.