更新于：2024-05-01

INF-λ2

interferon lambda 2

更新于：2024-05-01

基本信息

别名

Cytokine Zcyto20、IFN-lambda-2、IFNL2

+ [6]

简介

Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.

关联

100 项与 INF-λ2 相关的临床结果

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100 项与 INF-λ2 相关的转化医学

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0 项与 INF-λ2 相关的专利（医药）

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281

项与 INF-λ2 相关的文献（医药）

2024-01-31·FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Interleukin 28A aggravates Con A-induced acute liver injury by promoting the recruitment of M1 macrophages.

Article

作者: Junfeng Zhang ; Dalei Cheng ; Hui Zhang ; Zhihong Liu ; Min Gao ; Li Wei ; Fenglian Yan ; Chunxia Li ; Lin Wang ; Guanjun Dong ; Changying Wang ; Mingsheng Zhao ; Yuanbo Zhu ; Huabao Xiong

Immune-mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin-28A (IL-28A), a member of the IL-10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL-28A, its role in immune-mediated acute injury remains unclear. The present study investigated the role of IL-28A in concanavalin A (Con A)-induced acute immune liver injury. After Con A injection in mice, IL-28A level significantly increased. IL-28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL-28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL-28A-deficiency group than in the wild-type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL-28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-12, IL-6, and IL-1β, by M1 macrophages decreased significantly in the IL-28A-deficiency group. Western blotting demonstrated that IL-28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL-28A deletion plays an important protective role in the Con A-induced acute liver injury model and IL-28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF-κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune-related hepatic injury.

2023-12-19·Journal of neuroinflammation

27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice.

Article

作者: Tao Wang ; Wenjing Feng ; Mengwei Ju ; Huiyan Yu ; Zhiting Guo ; Xuejing Sun ; Kexin Yang ; Miao Liu ; Rong Xiao

BACKGROUND:

Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC).

METHODS:

100 individuals were recruited into the nested case-control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected.

RESULTS:

Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-β1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-β (Aβ) and the precursor of amyloid A amyloidosis-serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-β1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline.

CONCLUSIONS:

Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.

2023-11-27·Biomedicines

The Serum ACE2, CTSL, AngII, and TNFα Levels after COVID-19 and mRNA Vaccines: The Molecular Basis.

Article

作者: Mina Pencheva ; Martina Bozhkova ; Yordan Kalchev ; Steliyan Petrov ; Alexandra Baldzhieva ; Teodora Kalfova ; Valentin Dichev ; Donka Keskinova ; Silvia Genova ; Mariya Atanasova ; Mariana Murdzheva

BACKGROUND:

The SARS-CoV-2 virus as well as the COVID-19 mRNA vaccines cause an increased production of proinflammatory cytokines.

AIM:

We investigated the relationship between ACE2, CTSL, AngII, TNFα and the serum levels of IL-6, IL-10, IL-33, IL-28A, CD40L, total IgM, IgG, IgA and absolute count of T- and B-lymphocytes in COVID-19 patients, vaccinees and healthy individuals.

METHODS:

We measured the serum levels ACE2, AngII, CTSL, TNFα and humoral biomarkers (CD40L, IL-28A, IL-10, IL-33) by the ELISA method. Immunophenotyping of lymphocyte subpopulations was performed by flow cytometry. Total serum immunoglobulins were analyzed by the turbidimetry method.

RESULTS:

The results established an increase in the total serum levels for ACE2, CTSL, AngII and TNFα by severely ill patients and vaccinated persons. The correlation analysis described a positive relationship between ACE2 and proinflammatory cytokines IL-33 (r = 0.539) and CD40L (r = 0.520), a positive relationship between AngII and CD40L (r = 0.504), as well as between AngII and IL-33 (r = 0.416), and a positive relationship between CTSL, total IgA (r = 0.437) and IL-28A (r = 0.592). Correlation analysis confirmed only two of the positive relationships between TNFα and IL-28A (r = 0.491) and CD40L (r = 0.458).

CONCLUSIONS:

In summary, the findings presented in this study unveil a complex web of interactions within the immune system in response to SARS-CoV-2 infection and vaccination.

项与 INF-λ2 相关的新闻（医药）

2022-11-28

·药研网

IL-10：荆棘丛生之路

IL-10自1989年首次被发现，针对它的学术研究已进行了三十余年，但时至今日，它在药物研发领域仍然是个“冷门”。01靶点概述白介素10(IL-10)最初被描述为Th2细胞细胞因子。包括IL-19、IL-20、IL-22、IL-24、IL-26、IL-28A、IL-28B和IL-29等，这些与IL-10具有相似蛋白质结构和受体复合物的细胞因子也被称为IL-10家族细胞因子。IL-10是一种现在被认为是复杂的多效的细胞因子，能够影响上皮功能并参与过敏和感染等炎症疾病，具有重要的免疫调节功能。其主要由抗原呈递细胞分泌，如活化的T细胞、单核细胞、B细胞和巨噬细胞。在生物功能形式中，IL-10以同源二聚体的形式存在，与四聚体异二聚体IL-10R结合并诱导下游信号转导。功能性IL-10R复合体是由两个配体结合亚基IL-10Rα（IL-10R1）和两个辅助信号亚基IL-10Rβ（IL-10R2）组成的四聚体。[1]02信号通路IL-10与IL-10Rα胞外结构域的结合激活了受体相关的JAK1和TYK2的磷酸化，然后IL-10Rα链胞内结构域的特异性酪氨酸残基Y446和Y496被磷酸化，这些酪氨酸残基(及其侧肽序列)就会成为潜在转录因子STAT3的临时停靠点。STAT3通过其SH2结构域与这些位点结合，继而被受体相关的JAKs酪氨酸磷酸化，继而STAT3二聚化入核，激活核内基因的转录翻译，从而增加了抗凋亡和细胞周期进展基因的转录。IL-10信号通路示意图[2]此外，IL-10还可以激活PI3K及其下游底物p70S6K和Akt/PKB。尽管IL-10的抗炎作用不是通过PI3K介导的，但IL-10促进星形胶质细胞存活或诱导肥大细胞增殖的能力取决于PI3K的激活。IL-10还会干扰LPS及其受体TLR4的下游信号p38/MAPK通路，从而抑制肿瘤坏死因子的翻译通路（TNF-mRNA）。在一些研究中，IL-10促进癌细胞生长和存活，包括非霍奇金淋巴瘤、伯基特淋巴瘤和非小细胞肺癌，IL-10过表达与SLE，结核病相关，而炎症性肠病、银屑病、哮喘、类风湿性关节炎等疾病与IL-10缺乏相关。03竞争格局2018年，礼来斥资16亿美元收购ARMO Biosciences，获得其下IL-10项目pegilodecakin。2019年，其治疗胰腺癌的III期临床因未达主要终点而宣告失败，之后，其治疗肺癌的两个II期临床也终止，一番挣扎之后，这款名噪一时的候选药消失得悄无声息。同年，Biotest AG宣布其人源化IL-10单抗BT-063治疗系统性红斑狼疮的2期临床试验结果达主要终点，BT-063在自免疫疾病治疗领域大有可为。然而至今，官网管线中已不见其身影。此外，包括默沙东的MK-1966、Y-Biologics的YBL010和Cytonus Therapeutics的CA-IL10等十几条管线均已终止开发，不了了之。时至今日，IL-10赛道中多家公司或机构纷纷进入，又纷纷离开，仍然在这条赛道上奔跑的选手已所剩无几。AMT-101是一种新型的、具有消化道选择性的的口服重组生物融合蛋白——人白细胞介素10（hIL-10），主要用于治疗炎症性肠病和系统性炎症适应症。该药物采用AMT的专有平台设计，旨在利用肠道内自然生物运输机制的力量，使其能够穿过肠道上皮屏障，直接与肠道组织中丰富的免疫环境中的细胞相互作用。今年7月公布的治疗中度至重度溃疡性结肠炎（UC）的2期顶线结果显示，对于主要终点来说，AMT-101联合阿达木单抗治疗组的临床缓解率（31.8%）与对照组安慰剂联合阿达木单抗治疗组（临床缓解率33.3%）相比，并没有表现出更好的疗效优势。但是在UC病程＜5年的患者中，AMT-101联合治疗的临床缓解率为43.8%，对照组15.4%，疗效显著。Dekavil (F8IL10)由F8抗体与IL10融合组成，它对纤连蛋白的EDA结构域具有特异性，能选择性地定位在各种炎症的炎症组织中。XT-150是一种局部注射的质粒DNA基因疗法，表达IL-10v（一种IL-10的专有改良变体），以解决病理性炎症和疼痛。XT-150与目前的标准治疗相比，大大增加了其效果的持续时间。小结：IL-10自发现至今已30多年，在这条布满荆棘的道路上，有人倒下，也有人在艰难前行，致敬这些荆棘途中形单影只的孤勇者，也期待这些药物后续会有更好的进展。扫码查询现货细胞系参考：1. doi:10.1111/febs.162072.https://www.thermofisher.cn/cn/zh/home/life-science/antibodies/antibodies-learning-center/antibodies-resource-library/cell-signaling-pathways/il-10-pathway.html3. doi: 10.3389/fimmu.2022.9479834. doi: 10.1084/jem.201904185. doi: 10.1080/2162402X.2021.20035336. 各企业官网往期推荐PROTAC全球布局一览Fierce Biotech丨2022年医药企业裁员追踪盘点国产PD-1销售盘点点击下方“药研网”，关注更多精彩内容

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