更新于：2024-11-01

IL20RB

更新于：2024-11-01

基本信息

别名

DIRS1、Fibronectin type III domain containing 6、FNDC6

+ [10]

简介

The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL22RA1/IL20RB dimer is a receptor for IL20 and IL24.

关联

项与 IL20RB 相关的药物

CN116925220

专利挖掘

靶点

IL20RB

作用机制-

在研机构

中国科学院上海营养与健康研究所

原研机构

中国科学院上海营养与健康研究所

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IL20RB 相关的临床结果

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100 项与 IL20RB 相关的转化医学

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0 项与 IL20RB 相关的专利（医药）

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192

项与 IL20RB 相关的文献（医药）

2024-12-01·Cellular and Molecular Life Sciences

CD200R activation on naïve T cells by B cells induces suppressive activity of T cells via IL-24

Article

作者: Chiang, Bor-Luen ; Chu, Kuan-Hua

AbstractCD200 is an anti-inflammatory protein that facilitates signal transduction through its receptor, CD200R, in cells, resulting in immune response suppression. This includes reducing M1-like macrophages, enhancing M2-like macrophages, inhibiting NK cell cytotoxicity, and downregulating CTL responses. Activation of CD200R has been found to modulate dendritic cells, leading to the induction or enhancement of Treg cells expressing Foxp3. However, the precise mechanisms behind this process are still unclear. Our previous study demonstrated that B cells in Peyer’s patches can induce Treg cells, so-called Treg-of-B (P) cells, through STAT6 phosphorylation. This study aimed to investigate the role of CD200 in Treg-of-B (P) cell generation. To clarify the mechanisms, we used wild-type, STAT6 deficient, and IL-24 deficient T cells to generate Treg-of-B (P) cells, and antagonist antibodies (anti-CD200 and anti-IL-20RB), an agonist anti-CD200R antibody, CD39 inhibitors (ARL67156 and POM-1), a STAT6 inhibitor (AS1517499), and soluble IL-20RB were also applied. Our findings revealed that Peyer’s patch B cells expressed CD200 to activate the CD200R on T cells and initiate the process of Treg-of-B (P) cells generation. CD200 and CD200R interaction triggers the phosphorylation of STAT6, which regulated the expression of CD200R, CD39, and IL-24 in T cells. CD39 regulated the expression of IL-24, which sustained the expression of CD223 and IL-10 and maintained the cell viability. In summary, the generation of Treg-of-B (P) cells by Peyer’s patch B cells was through the CD200R-STAT6-CD39-IL-24 axis pathway.

2024-05-01·Pharmacological Research

IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation

Article

作者: Gao, Shaoyan ; Li, Xiaohe ; Zhu, Jingyan ; Zhang, Huizhe ; Xia, Qin ; Zhao, Ruixi ; Liu, Bowen ; Yang, Cheng ; Zhou, Honggang ; Xu, Aiguo ; Jiang, Haixia ; Jiang, Qiuyan ; Xu, Zuojun

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18…), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.

2024-04-01·Inflammation Research

Interleukin-19 enhances eosinophil infiltration through upregulation of epithelium-derived RANTES expression via the ERK/NF-κB signalling pathway in patients with eosinophilic CRSwNP

Article

作者: Zhang, Gehua ; Huang, Weiqiang ; Wu, Haotian ; Li, Xia ; Huang, Zizhen ; Chang, Lihong ; Zhang, Yana ; Chen, Xiaohong ; Lai, Xiaoping ; Li, Yue

BACKGROUDThe recurrence rate of chronic rhinosinusitis with nasal polyps (CRSwNP) is positively correlated with eosinophil infiltration. Increased interleukin (IL)-19 and eosinophil chemokine RANTES levels have been reported in patients with CRSwNP. This study aimed to clarify the role of IL-19 in mediating RANTES expression and eosinophilic infiltration in eosinophilic CRSwNP (Eos CRSwNP).METHODSNasal tissue samples were obtained from patients with CRSwNP and controls. The expression of IL-19, its receptors, ECP, and RANTES in tissues was investigated. Primary human nasal epithelial cells (HNECs) and nasal polyp tissue blocks were cultured, then stimulated by IL-19; ERK phosphorylation, NF-κB pathway activation, RANTES level, eosinophils migration and infiltration were detected using RT-qPCR, ELISA, western blotting, HE, immunohistochemistry, immunofluorescence staining, confocal microscopy, and transwell migration assay.RESULTSThe expression of IL-19 and its receptors (IL-20R1/IL-20R2), eosinophil cationic protein, and RANTES in nasal tissues from patients with Eos CRSwNP was significantly increased compared to that in non-Eos CRSwNP and control subjects. IL-19 co-localized with RANTES in nasal tissues and significantly elevated RANTES expression in HNECs. IL-19-blocking antibody and siRNA knockdown of IL-20R1 ameliorated the effect of IL-19 on RANTES secretion in HNECs. Moreover, IL-19-induced RANTES upregulation was associated with the activation of the ERK and NF-κB pathways. NF-κB activation was mediated by the ERK pathway in IL-19-treated HNECs, and IL-19 enhanced eosinophil infiltration in nasal polyp tissue blocks.CONCLUSIONSOur findings indicate that IL-19 promotes RANTES expression via the ERK/NF-κB pathway in HNECs and is implicated in eosinophil infiltration in patients with Eos CRSwNP.

项与 IL20RB 相关的新闻（医药）

2022-10-12

·生物谷

JCI：中国科学家发现肺癌骨转移的新机制！

此项工作首次阐明了肺癌骨转移当中破骨细胞对肺癌细胞的直接调节作用，并证实靶向调控IL20RB可以明显抑制肺癌骨转移。这一发现为肺癌骨转移的治疗提供了全新的干扰靶点。骨骼是肺癌最为频繁的转移靶部位。除了较高的死亡率，骨转移还给患者造成身体上的折磨，包括疼痛和骨折，大大降低了患者的生活质量[1-3]。然而，肺癌骨转移的调控机制仍不明朗。由于骨骼组织具有不同于其他软体组织的特性，肿瘤向其转移的调控机制也具有一定的特性[4]。在肿瘤骨转移的过程中，肿瘤细胞先是通过分泌细胞因子促进破骨细胞成熟。随后，破骨细胞又通过破坏骨骼基质，从骨基质中释放出大量促进肿瘤生长的细胞因子。作为肿瘤细胞骨转移的重要“帮凶”，破骨细胞与肿瘤细胞之间形成一个相互促进恶性循环（Vicious cycle），在肺癌骨转移中发挥关键作用 [5-7]。先前的研究普遍认为破骨细胞是通过“破骨”这一功能间接参与肿瘤骨转移，然而，关于破骨细胞能否直接作用于癌细胞目前仍不明朗。因此，进一步阐明破骨细胞与肺癌细胞之间相互作用的机制，从而为肺癌骨转移提供新的治疗靶点，具有重要的临床意义。近日，中国科学院上海营养与健康研究所胡国宏教授、上海胸科医院姚烽医生以及上海第十人民医院符达研究员团队合作，在Journal of Clinical Investigation上发表了有关肺癌骨转移发生机制及治疗策略的重要研究成果[8]。该研究团队证实，肺癌通过诱导破骨细胞分泌白介素19（IL-19），并作用于肺癌细胞表面的白介素受体20亚基B（IL20RB），进而促进肺癌细胞的增殖和骨转移。此发现为肺癌骨转移的治疗提供了新的思路。论文首页图接下来，我们就一起来来看看这个研究是如何展开的。首先，研究人员使用单细胞克隆技术，体外筛选得到了一系列具有不同骨转移能力的肺癌细胞系，并将具有高骨转移能力的肺癌细胞注射至小鼠体内形成肿瘤。通过对高骨转移能力和低骨转移能力的细胞株进行转录组测序技术，研究人员发现IL20RB在高骨转移能力的肺癌细胞株中显著高表达。除此之外，研究人员还在肺癌患者的临床数据库中发现，IL20RB与临床患者肺癌骨转移的发生及较差的预后密切相关。 IL20RB与临床患者肺癌骨转移的发生及较差的预后相关随后，研究人员分别构建了IL20RB稳定敲除和过表达的肺癌细胞系，并将这些肺癌细胞注射至小鼠成瘤后发现，IL20RB过表达明显促进了肺癌骨转移，却对肺癌向其他部位的转移没有影响。此外，研究人员还发现，IL20RB过表达显著上调了肺癌细胞的增殖能力。接下来，研究人员对IL20RB促进肺癌骨转移的机制进行进一步探索。以往的研究发现，肺癌细胞常通过诱导破骨细胞的成熟，从而促进破骨细胞向骨转移[9]。出人意料的是，研究人员对骨转移病灶中成熟破骨细胞进行检测发现，肺癌中IL20RB并不影响破骨细胞的成熟。 IL20RB没有影响破骨细胞的成熟那么，IL20RB是通过何种机制促进肺癌骨转移呢？研究人员猜测破骨细胞与肺癌可能存在一个相互作用的机制，于是用培养过破骨细胞的条件培养基（Oste-CM）培养肺癌细胞后发现，与对照组相比，IL20RB过表达的肺癌细胞表现出更强的增殖能力。以上结果表明，肺癌细胞表面的IL20RB介导了破骨细胞对肺癌细胞增殖的促进作用。先前的研究表明，IL-19，IL20及IL-24是IL20RB的主要配体[10]。研究人员发现，只有IL-19在破骨细胞中表达较高。十分有趣的是，对肺癌骨转移的临床样本进行免疫荧光染色发现，IL20RB大量表达于肿瘤细胞上，而IL-19则广泛存在于肿瘤微环境细胞中，提示破骨细胞来源的IL-19可能是促进肺癌细胞生长的关键因子。 IL20RB及IL-19在肺癌骨转移肿瘤中的定位为了证实这一猜想，研究人员使用IL-19的中和抗体预处理Oste-CM以清除其中的IL-19，发现这一处理明显抑制了肺癌肿瘤细胞的生长，而使用IL-19重组蛋白却可以明显促进肺癌细胞系的生长。研究人员用肺癌细胞的条件培养基（TC-CM）培养破骨细胞后发现，TC-CM也可以明显促进破骨细胞IL-19的分泌。进一步的机制探究表明，肺癌细胞可以通过分泌粒细胞-巨噬细胞集落刺激因子（GM-CSF）作用于破骨细胞，诱导其分泌IL-19，进而促进肿瘤细胞自身的增殖。研究人员还在IL-19的敲除小鼠中发现，与野生型小鼠相比，IL-19敲除的小鼠中过表达IL20RB的肺癌细胞骨转移的发生没有增加。此外，通过分离野生型和IL-19敲除小鼠的骨髓细胞并诱导为破骨细胞后，研究人员发现，IL-19敲除小鼠破骨细胞的条件培养基几乎无法诱导肺癌细胞的增殖和类器官的形成。以上结果表明，肺癌微环境中衍生的IL-19和肺癌细胞自身表达的IL20RB对肺癌骨转移的发生至关重要。进一步的机制探索发现，破骨细胞所分泌的IL-19作用于肺癌细胞表面的IL20RB，激活JAK1-STAT3信号通路，进而促进了肿瘤细胞的增殖和转移。使用STAT3的抑制剂可以明显抑制IL20RB介导的肿瘤增殖，并减少骨转移的发生。敲低SATA3抑制了IL20RB的促肺癌骨转移的作用最后，研究人员发现，使用靶向IL20RB的中和抗体LTMA1G11可以破坏破骨细胞与肺癌细胞相互促进的“恶性循环”，有效抑制肺癌骨转移的发生。文章机制图总的来说，此项工作首次阐明了肺癌骨转移当中破骨细胞对肺癌细胞的直接调节作用，并证实靶向调控IL20RB可以明显抑制肺癌骨转移。这一发现为肺癌骨转移的治疗提供了全新的干扰靶点。参考文献： [1] Ghilardi JR, Röhrich H, Lindsay TH, et al. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci. 2005;25(12):3126-3131. doi:10.1523/JNEUROSCI.3815-04.2005 [2] Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain. 1997;69(1-2):1-18. doi:10.1016/s0304-3959(96)03267-8 [3] Sevcik MA, Ghilardi JR, Peters CM, et al. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain. 2005;115(1-2):128-141. doi:10.1016/j.pain.2005.02.022 [4] Yin JJ, Pollock CB, Kelly K. Mechanisms of cancer metastasis to the bone. Cell Res. 2005;15(1):57-62. doi:10.1038/sj.cr.7290266 [5] Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98-101. [6] Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537-549. doi:10.1016/s1535-6108(03)00132-6 [7] Duivenvoorden WC, Hirte HW, Singh G. Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells. Clin Exp Metastasis. 1999;17(1):27-34. doi:10.1023/a:1026404227624 [8] He Y, Luo W, Liu Y, et al. IL20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer [published online ahead of print, 2022 Aug 25]. J Clin Invest. 2022;e157917. doi:10.1172/JCI157917 [9] Muscarella AM, Aguirre S, Hao X, Waldvogel SM, Zhang XH. Exploiting bone niches: progression of disseminated tumor cells to metastasis. J Clin Invest. 2021;131(6):e143764. doi:10.1172/JCI143764 [10] Parrish-Novak J, Xu W, Brender T, et al. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem. 2002;277(49):47517-47523. doi:10.1074/jbc.M205114200