IMMUNITY
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2024
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IF 25.5
Jiping Sun,Youqin Zhang,Qingbing Zhang,Lin Hu,Linfeng Zhao,Hongdong Wang,Yue Yuan,Hongshen Niu,Dongdi Wang,Huasheng Zhang,Jianyue Liu,Xujiao Feng,Xiaohui Su,Ju Qiu,Jing Sun,Heping Xu,Catherine Zhang,Kathleen Wang,Yan Bi,Edgar G. Engleman,Lei Shen
Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.
研究领域:
免疫学
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代谢生物学
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医学
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DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2025
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IF 3
Jianbin Xiong,Jian Song,Xing Jiang,Zhuanzhuan Huang,Yijie Zhang
Chronic pancreatitis (CP) is a progressive inflammatory disorder with no effective treatment, which underscores the urgent need for novel therapeutic strategies. In this study, single-cell sequencing data retrieved from the Gene Expression Omnibus (GEO) database revealed that Prkcq and IL-4 were highly induced in group 2 innate lymphoid cells (ILC2s), while Mitf and Tgm2 were highly expressed in tissue-resident macrophages (TRMs). A mouse model of CP was established using dibutyltin dichloride (DBTC), and pathological evaluations via H&E, Masson, and Sirius Red staining confirmed typical features of CP, including acinar atrophy, inflammatory cell infiltration, and increased fibrosis. Notably, the numbers of ILC2s and TRMs in pancreatic tissues were significantly elevated in DBTC-treated mice. Functional experiments showed that the Prkcq knockdown in ILC2s suppressed the expression of IL-4, IL-5 and IL-13, while in TRMs, the transcription factor Mitf upregulated Tgm2 expression. In CP mice, Prkcq knockdown reduced TRM abundance, ultimately alleviating pancreatic fibrosis. Collectively, this study identifies Prkcq as a key regulator of CP by modulating TRM populations.
研究领域:
免疫学
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细胞生物学
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分子生物学
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病理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Demengjie Le,Hailin Wang,Zhiwen Zhang,Ruoxi Liao,Yingjie Zhao,Jiarui Zhang,Yu Wang,Xinyu Lu,Zhiqi Hu,Xuan Wang,Ziwei Hu,Yuyang Gan
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by intense pruritus, xerosis, and erythema. Its pathogenesis involves hyperactivation of type 2 innate lymphoid cells (ILC2s) and excessive accumulation of interleukin-31(IL-31). Moreover, over-colonization of Staphylococcus aureus exacerbates inflammation and skin barrier damage. Targeting pruritus and restoring immune and microbiota homeostasis are crucial for AD management. Herein, we developed a near-infrared-responsive anti-pruritic motor for AD treatment. The motor is encapsulated in a hybrid membrane armor composed of Cutibacterium acnes cell wall and keratinocytes membrane, enabling targeted ILC2 downregulation for immunomodulation and effective clearance of free IL-31 for pruritus relief. Inside the armor, a janus bowl-shaped polydopamine (Bowl–PDA) exhibits NIR-responsive motion under NIR irradiation, significantly enlarging the clearance area of the membrane armor. Concurrently, Zn 2+ released from the system effectively inhibits Staphylococcus aureus colonization. This integrated motor significantly reduced erythema and scratching-related indices, restored skin barrier and microbiota function, normalized ILC homeostasis by downregulating IL-33-ILC2 axis and suppressed IL-31–TRPV1 pruritic signaling. Collectively, this strategy demonstrates robust anti-pruritic efficacy, coordinated remodeling of immune and microbiota homeostasis, offering a promising platform for precision AD therapy. Schematic diagram: S. aureus over-colonization, ILC2 hyperactivation, and excessive IL-31–IL-31Ra–TRPV1 signaling drive skin inflammation and pruritus in atopic dermatitis. Under NIR irradiation, NIR-responsive motion of janus Bowl–PDA@Zn motors significantly enlarging the clearance area, enabled outer layer hybrid C. acnes cell wall–keratinocyte membrane extensively suppress ILC2 activation, eliminate IL-31, and release antibacterial Zn 2+ among AD lesion, thereby restoring cutaneous immune and microbial homeostasis, achieve antiprurtic therapeutic effect. Download: Download high-res image (157KB) Download: Download full-size image
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Meng-Ke Liu,Juan-Juan Tang,Hao Li,Xu-Yang Chen,Jun-Ling Cai,Gui-Ying Lin,Kan-Yao Chen,Zhi-Peng Liu,Xiao-Fang Ji,Zhong-Jin Yang,Zi Li
Artemisitene (ATT), an artemisinin (ART) analog retaining the endoperoxide moiety and incorporating an additional α, β-unsaturated carbonyl structure, exhibits enhanced biological activities. However, its therapeutic effects on liver fibrosis remain unclear. In this study, we demonstrated that ATT significantly alleviated liver inflammation and fibrosis induced by carbon tetrachloride (CCL 4 ) in mice. ATT treatment markedly reduced the count of neutrophils in the liver, as well as macrophages in both the liver and spleen. Additionally, the frequencies of Th2 and Th17 cells were significantly lowered, while Th1 cells frequency and the Th1/Th2 index were notably increased. The frequency of ILC2 cells, correlated with ST2 and IL-33 expression levels, was also significantly lowered. Consistently, ATT inhibited NLRP3 inflammasome activation, which was positively associated with AST and ALT levels, and with the count of Neutrophils, macrophages, and ILC2 cells, but negatively correlated with Th1frequeny. Furthermore, liver fibrosis severity showed a significant positive correlation with neutrophil and Th17 cell counts in the liver, and a negative correlation with Th1 cell count and the Th1/Th2 index. Therefore, ATT alleviated CCL 4 -induced mice liver fibrosis through NLRP3 inflammasome inhibition and immunomodulation.
研究领域:
药理学
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免疫学
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肝病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
·
IF 6.7
Hui-Hui Guo,Yan-Xing Han,Xiao-Juan Rong,Zhen Shen,Hao-Ran Shen,Ling-Fei Kong,Yun-Dan Guo,Ji-Zhou Li,Bo Xu,Tian-Le Gao,Lu-Lu Wang,Cai Tie,Jian-Dong Jiang
Background Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. Conclusions The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
研究领域:
药理学
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免疫学
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微生物学
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呼吸医学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-33
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IF 10.6
Liu Jianyu,Wang Meiqun,Tian Xiaoyan,Wu Shuhong,Peng Haisen,Zhu Yaqiong,Liu Yuehui
Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR. Graphical Abstract
研究领域:
免疫学
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
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