ILC2s are implicated in asthma pathogenesis, but little is known about the mechanisms underlying their accumulation in airways.We investigated the time course of ILC2 accumulation in different tissues in murine models...ILC2s are implicated in asthma pathogenesis, but little is known about the mechanisms underlying their accumulation in airways.We investigated the time course of ILC2 accumulation in different tissues in murine models of asthma induced by a serial per-nasalchallenge with ovalbumin (OVA), house dust mice (HDM), IL-25 and IL-33 and explored the potential roles of ILC2-attractingchemokines in this phenomenon. Flow cytometry was used to enumerate ILC2s at various time points. The effects of cytokines andchemokines on ILC2 migration were measured in vitro using a chemotaxis assay and in vivo using small animal imaging. Comparedwith saline and OVA challenge, both IL-25 and IL-33 challenge alone induced significant accumulation of ILC2s in the mediastinallymph nodes, lung tissue and bronchoalveolar lavage fluid of challenged animals, but with a distinct potency and kinetics. In vitro,IL-33 and CXCL16, but not IL-25 or CCL25, directly induced ILC2 migration. Small animal in vivo imaging further confirmed that asingle intranasal provocation with IL-33 or CXCL16 was sufficient to induce the accumulation of ILC2s in the lungs followinginjection via the tail vein. Moreover, IL-33-induced ILC2 migration involved the activation of ERK1/2, p38, Akt, JNK and NF-κB, whileCXCL16-induced ILC2 migration involved the activation of ERK1/2, p38 and Akt. These data support the hypothesis that epitheliumderived IL-25 and IL-33 induce lung accumulation of ILC2s, while IL-33 exerts a direct chemotactic effect in this process. AlthoughILC2s express the chemokine receptors CXCR6 and CCR9, only CXCL16, the ligand of CXCR6, exhibits a direct chemoattractanteffect.展开更多
目的:探讨外周血单一核细胞(PBMC)中胸腺基质淋巴细胞生成素(TSLP)和白介素(IL)-25水平变化在湿疹发病机.制中的作用。方法:采用反转录-聚合酶链反应(RT-PCR)方法,对80例急性期湿疹患者和40例正常对照者PBMC中TSLP、IL-25mRNA的表达量...目的:探讨外周血单一核细胞(PBMC)中胸腺基质淋巴细胞生成素(TSLP)和白介素(IL)-25水平变化在湿疹发病机.制中的作用。方法:采用反转录-聚合酶链反应(RT-PCR)方法,对80例急性期湿疹患者和40例正常对照者PBMC中TSLP、IL-25mRNA的表达量进行分析。用△CT法进行相对定量分析,△CT值与mRNA的表达量成反比。按照湿疹面积及严重度指数(EASI)评分标准对湿疹患者进行评分。运用SPSS13.0统计软件包进行统计。结果:湿疹患者PBMC中。TSLP和IL-25 mRNA表达水平明显高于正常对照组(二者△CT值分别为:1.03±0.43 vs 1.65±.0.87,1.03±0.25 vs 1.。74±0.93,P<0.05),且湿疹患者PBMC中TSLP、IL-25mRNA的水平与EASI评分成正相关(r值分别为:-0.418和-0.941,P<0.05);湿疹患者PBMC中TSLP和IL-25mRNA表达水平与嗜酸『生粒细胞计数(EOS)呈正相关(r值分别为:-0.53和--0.46,P<0.05)。结论:湿疹患者PBMC中TSLP和IL,-25mRNA水平升高,且与皮损的面积及严重程度有关,说明TSLP和IL-25可能参与了湿疹的致病过程;湿疹患者PBMC中TSLP和IL-25 mRNA水平与EOS计数之间呈明显正相关性,因此,EOS计数的变化可以作为推测湿疹患者严重度指数的指标,有助于湿疹的疗效判断。展开更多
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells,especially macrophages.Immune molecules,including some cytokines,h...Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells,especially macrophages.Immune molecules,including some cytokines,have a close relationship with metabolism.Interleukin(IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction;however,its role and mechanisms in lipid metabolism remain to be extensively clarified.Human serum and liver biopsy specimens,high-fat diet-induced obesity mice and DB/DB(Lepr−/−)animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases(NAFLD).To observe the role of IL-25 in lipid metabolism,model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo,whereas bone marrow-derived macrophages,the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro.IL-25 was decreased in NAFLD patients and obese mice.In addition,IL-25 reduced body weight gain and lipid accumulation,enhanced lipid uptake by macrophages and increased the expression of lipolysis andβ-oxidation enzymes via alternatively activating macrophages.IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages.Furthermore,IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD+/NADH and ATP.In conclusion,IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity,highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.展开更多
基金the National Natural Science Foundation of China(81373177,81471594,and 81700026).
文摘ILC2s are implicated in asthma pathogenesis, but little is known about the mechanisms underlying their accumulation in airways.We investigated the time course of ILC2 accumulation in different tissues in murine models of asthma induced by a serial per-nasalchallenge with ovalbumin (OVA), house dust mice (HDM), IL-25 and IL-33 and explored the potential roles of ILC2-attractingchemokines in this phenomenon. Flow cytometry was used to enumerate ILC2s at various time points. The effects of cytokines andchemokines on ILC2 migration were measured in vitro using a chemotaxis assay and in vivo using small animal imaging. Comparedwith saline and OVA challenge, both IL-25 and IL-33 challenge alone induced significant accumulation of ILC2s in the mediastinallymph nodes, lung tissue and bronchoalveolar lavage fluid of challenged animals, but with a distinct potency and kinetics. In vitro,IL-33 and CXCL16, but not IL-25 or CCL25, directly induced ILC2 migration. Small animal in vivo imaging further confirmed that asingle intranasal provocation with IL-33 or CXCL16 was sufficient to induce the accumulation of ILC2s in the lungs followinginjection via the tail vein. Moreover, IL-33-induced ILC2 migration involved the activation of ERK1/2, p38, Akt, JNK and NF-κB, whileCXCL16-induced ILC2 migration involved the activation of ERK1/2, p38 and Akt. These data support the hypothesis that epitheliumderived IL-25 and IL-33 induce lung accumulation of ILC2s, while IL-33 exerts a direct chemotactic effect in this process. AlthoughILC2s express the chemokine receptors CXCR6 and CCR9, only CXCL16, the ligand of CXCR6, exhibits a direct chemoattractanteffect.
文摘目的:探讨外周血单一核细胞(PBMC)中胸腺基质淋巴细胞生成素(TSLP)和白介素(IL)-25水平变化在湿疹发病机.制中的作用。方法:采用反转录-聚合酶链反应(RT-PCR)方法,对80例急性期湿疹患者和40例正常对照者PBMC中TSLP、IL-25mRNA的表达量进行分析。用△CT法进行相对定量分析,△CT值与mRNA的表达量成反比。按照湿疹面积及严重度指数(EASI)评分标准对湿疹患者进行评分。运用SPSS13.0统计软件包进行统计。结果:湿疹患者PBMC中。TSLP和IL-25 mRNA表达水平明显高于正常对照组(二者△CT值分别为:1.03±0.43 vs 1.65±.0.87,1.03±0.25 vs 1.。74±0.93,P<0.05),且湿疹患者PBMC中TSLP、IL-25mRNA的水平与EASI评分成正相关(r值分别为:-0.418和-0.941,P<0.05);湿疹患者PBMC中TSLP和IL-25mRNA表达水平与嗜酸『生粒细胞计数(EOS)呈正相关(r值分别为:-0.53和--0.46,P<0.05)。结论:湿疹患者PBMC中TSLP和IL,-25mRNA水平升高,且与皮损的面积及严重程度有关,说明TSLP和IL-25可能参与了湿疹的致病过程;湿疹患者PBMC中TSLP和IL-25 mRNA水平与EOS计数之间呈明显正相关性,因此,EOS计数的变化可以作为推测湿疹患者严重度指数的指标,有助于湿疹的疗效判断。
基金supported by the National Nature Science Foundation of China:81272338,81272515,81370945,81471033,81570871,81570764 and 81600641the National Key Sci-Tech Special Project of China:2013ZX09102-053,2015GKS-355+7 种基金the Program for Doctoral Station in University:20130171110053the Key Project of the Nature Science Foundation of Guangdong Province,China:2015A030311043,2016A030311035the Guangdong Natural Science Fund:2014A020212023,2014A030313073,2015A030313103 and 2015A030313029the Guandong Science and Technology Project(2014A020212023,2015B090903063 and 2016A020214001)the Guangzhou Science and Technology Project:2014J4100162,201508020033 and 201510010052the Pearl River Nova Program of Guangzhou Municipality,China,Grant Number:201610010186the Chang jiang Scholars and Innovative Research Team in University:985 project PCSIRT 0947the Fundamental Research Funds for the Central Universities of China(Youth Program 13ykpy06,16ykpy24 and 31610046).
文摘Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells,especially macrophages.Immune molecules,including some cytokines,have a close relationship with metabolism.Interleukin(IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction;however,its role and mechanisms in lipid metabolism remain to be extensively clarified.Human serum and liver biopsy specimens,high-fat diet-induced obesity mice and DB/DB(Lepr−/−)animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases(NAFLD).To observe the role of IL-25 in lipid metabolism,model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo,whereas bone marrow-derived macrophages,the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro.IL-25 was decreased in NAFLD patients and obese mice.In addition,IL-25 reduced body weight gain and lipid accumulation,enhanced lipid uptake by macrophages and increased the expression of lipolysis andβ-oxidation enzymes via alternatively activating macrophages.IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages.Furthermore,IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD+/NADH and ATP.In conclusion,IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity,highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.
