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This study investigated the mechanisms driving the induction and sustained presence of neutrophil extracellular traps (NETs) in the synovial microenvironment of rheumatoid arthritis (RA). Synovial tissue and fluid samples were collected from patients with RA and osteoarthritis (OA), and NET levels and cytokine concentrations were measured using a cytometric bead array and enzyme-linked immunosorbent assay (ELISA). The ability of interleukin-33 (IL-33) to induce NET formation was evaluated using quantitative assays, immunofluorescence staining, live-cell imaging, and electron microscopy. Coincubation experiments of NETs with fibroblast-like synovial cells (FLSs) were conducted, and a modified Transwell migration assay was designed to assess neutrophil migration. The role of IL-33 and NETs in RA progression was further investigated using a collagen antibody-induced arthritis (CAIA) mouse model. The results revealed an increase in NETs and IL-33 levels in the synovial fluid of RA patients, with a significant positive correlation between them. NET formation assays confirmed that IL-33 activates neutrophils to produce NETs and that neutrophils from RA patients exhibit increased responsiveness to IL-33 stimulation. Both in vitro and in vivo evidence has demonstrated that NETs stimulate FLSs to secrete IL-33 and the chemokine CXCL8 via Toll-like receptor 9, promoting further neutrophil recruitment and increasing NET production within the RA synovium. This study reveals a novel positive feedback loop involving NETs and FLSs that is mediated by IL-33 that increases NET accumulation in RA. Targeting IL-33 or NET formation and amplification may offer new therapeutic strategies for managing RA.

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기사명 저자명 페이지 원문 목차
Cytokine-overexpressing dendritic cells for cancer immunotherapy Joonsu Han, Hua Wang p. 2559-2568

ErbB4 precludes the occurrence of PTSD-like fear responses by supporting the bimodal activity of the central amygdala Kibong Sung, Min-Jae Jeong, Taesik Yoo, Jung Hoon Jung, Sumin Kang, Jong-Yeon Yoo, Hyun Jin Kim, Kyunghyun Park, Jung Hyun Pyo, Hyun-Yong Lee, Noah Koo, Soo-Hee Choi, Joung-Hun Kim p. 2703-2713

Neddylation steers the fate of cellular receptors Jun Bum Park, Min Young Lee, Jooseung Lee, Geon Ho Moon, Sung Joon Kim, Yang-Sook Chun p. 2569-2577

Hypothermic oxygenated perfusion inhibits CLIP1-mediated TIRAP ubiquitination via TFPI2 to reduce ischemia‒reperfusion injury of the fatty liver Pengpeng Yue, Xiaoyan Lv, Hankun Cao, Yongkang Zou, Jian You, Jun Luo, Zhongshan Lu, Hao Chen, Zhongzhong Liu, Zibiao Zhong, Yan Xiong, Xiaoli Fan, Qifa Ye p. 2588-2601

Astrocyte–neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury Qing Hu, Xun Wu, Chengxuan Guo, Tinghao Wang, Hao Guo, Jin Wang, Bodong Wang, Wenxing Cui, Hao Bai, Jinpeng Zhou ... [et al.] p. 2642-2658

Noncoding RNA as a crucial epigenetic modulator in the degeneration of the ligamentum flavum Yongzhao Zhao, Qian Xiang, Shuo Tian, Zhenquan Wu, Jialiang Lin, Longjie Wang, Zhuoran Sun, Weishi Li p. 2551-2558

VIM-AS1, which is regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma Su-hyang Han, Je Yeong Ko, Sungju Jung, Sumin Oh, Do Yeon Kim, Eunseo Kang, Myung Sup Kim, Kyung-Hee Chun, Kyung Hyun Yoo, Jong Hoon Park p. 2617-2630

Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT Hyejin Yeo, Ji-Hye Lim, Ji Eom, MinJeong Kim, Hyeji Kwon, Sang-Wook Kang, Youngsup Song p. 2690-2702

Distribution and impact of p16INK4A+ senescent cells in elderly tissues : a focus on senescent immune cell and epithelial dysfunction Soon Sang Park, Young-Kyoung Lee, Young Hwa Kim, So Hyun Park, Hee Young Kang, Jin Cheol Kim, Dong Jun Kim, Su Bin Lim, Gyesoon Yoon, Jang-Hee Kim, Yong Won Choi, Tae Jun Park p. 2631-2641

IL33-induced neutrophil extracellular traps (NETs) mediate a positive feedback loop for synovial inflammation and NET amplification in rheumatoid arthritis Jifeng Tang, Jinfang Xia, Huali Gao, Renquan Jiang, Lianbo Xiao, Huiming Sheng, Jinpiao Lin p. 2602-2616

(A) stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response Jumpei Ogura, Koji Yamanoi, Kentaro Ishida, Eijiro Nakamura, Shinji Ito, Naoki Aoyama, Yuki Nakanishi, Toshi Menju, Kosuke Kawaguchi, Yuko Hosoe, Mana Taki, Ryusuke Murakami, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai p. 2659-2672

EPRS1-mediated fibroblast activation and mitochondrial dysfunction promote kidney fibrosis Seung Seob Son, Hee Seul Jeong, Seong-Woo Lee, Eun Soo Lee, Jeong Geon Lee, Ji-Hye Lee, Jawoon Yi, Mi Ju Park, Min Sun Choi, Donghyeong Lee ... [et al.] p. 2673-2689

(The) anticancer effect of metformin targets VDAC1 via ER-mitochondria interactions-mediated autophagy in HCC Minjeong Ko, Jiho Kim, Raudah Lazim, Ju Yeon Lee, Jin Young Kim, Vijayakumar Gosu, Yoonji Lee, Sun Choi, Ho Jeong Kwon p. 2714-2725

TIGAR coordinates senescence-associated secretory phenotype via lysosome repositioning and α-tubulin deacetylation Hae Yun Nam, Seung-Ho Park, Geun-Hee Lee, Eun-Young Kim, SangEun Lee, Hyo Won Chang, Eun-Ju Chang, Kyung-Chul Choi, Seong Who Kim p. 2726-2738

GRIM-19-mediated induction of mitochondrial STAT3 alleviates systemic sclerosis by inhibiting fibrosis and Th2/Th17 cells Ha Yeon Jeong, Jin-Sil Park, Jeong Won Choi, Kun Hee Lee, Seung Cheon Yang, Hye Yeon Kang, Sang Hee Cho, Seon-Yeong Lee, A Ram Lee, Youngjae Park, Sung-Hwan Park, Mi-La Cho p. 2739-2746

Epigenetic reprogramming in mouse and human primordial germ cells Sun-Min Lee, M. Azim Surani p. 2578-2587

Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics Kyungtaek Park, Ji-Hyang Lee, Eunsoon Shin, Hye Yoon Jang, Woo-Jung Song, Hyouk-Soo Kwon, Yoo Sook Cho, Jong Eun Lee, Ian Adcock, Kian Fan Chung, Jeong Seok Lee, Sungho Won, Tae-Bum Kim p. 2755-2762

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