TICAM2

更新于：2025-05-07

基本信息

别名

MyD88-4、Putative NF-kappa-B-activating protein 502、TICAM-2

+ [9]

简介

Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes. Functions as a sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction (PubMed:16603631, PubMed:16757566, PubMed:25385819, PubMed:25825441). In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement (PubMed:25385819). Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adaptive immune response (PubMed:22685567). Forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria (PubMed:30883606).

关联

100 项与 TICAM2 相关的临床结果

登录后查看更多信息

100 项与 TICAM2 相关的转化医学

登录后查看更多信息

0 项与 TICAM2 相关的专利（医药）

登录后查看更多信息

147

项与 TICAM2 相关的文献（医药）

2025-04-01·Immunity, Inflammation and Disease

Quantitative Proteomic Analysis Indicates That Pggt1b Deficiency Promotes Cytokine Secretion in Resiquimod‐Stimulated Bone Marrow‐Derived Macrophages via the NF‐κB Pathway

Article

作者: Yu, Shanshan ; Hao, Zhimin ; Gu, Heng ; Long, Fangyuan ; Wei, Xuecui

ABSTRACTBackgroundPsoriasis is a systemic inflammatory skin disease mediated by the innate and adaptive immune systems. Recent studies have indicated that macrophages may contribute to the pathogenesis of psoriasis. However, the role of macrophage protein geranylgeranyl transferase type‐1β subunit (PGGT1B) in psoriasis is unclear. In this study, we aimed to establish how a reduction in Pggt1b expression in monocytes influences the onset and progression of psoriasis.MethodsMyeloid cell‐specific Pggt1b knockout mice were generated, and their bone marrow‐derived macrophages (BMDMs) were stimulated with resiquimod (R848) to mimic the psoriatic immune microenvironment. The proteomic analysis enabled us to identify 17 differentially expressed proteins associated with Pggt1b deficiency in the psoriasis macrophage model (folded change ≥ 1.3 and p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment was performed. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blot assays were used to verify the differentially expressed proteins and signaling pathways. Finally, an enzyme‐linked immunosorbent assay was used to verify the expression of the key inflammatory cytokine interleukin (IL)‐1β.ResultsIn total, six proteins (Dlgap5, Fas, Fnta, Nlrp3, Cd14, and Ticam2) were identified as hub proteins. Furthermore, we found that Pggt1b might mediate R848‐induced inflammation via the small G‐proteins Rac1 or Cdc42. We found that Pggt1b positively regulates pro‐inflammatory responses in R848‐stimulated BMDMs via the NF‐κB signaling pathway.ConclusionsThis study clarified that PGGT1B affected the synthesis of inflammatory cytokines via NF‐κB pathway and provided insights into the mechanisms underlying immune responses and inflammation.

2025-03-01·Cell Reports

Downstream signaling induced by several plant Toll/interleukin-1 receptor-containing immune proteins is stable at elevated temperature

Article

作者: Demont, Héloïse ; Sauvaget, Madeline ; Bernoux, Maud ; Deslandes, Laurent ; Culerrier, Raphaël ; Remblière, Céline

Plant immunity and, in particular, immune responses induced by nucleotide-binding leucine-rich repeat receptors (NLRs) are often dampened above the optimal plant's growth range, but the underlying molecular mechanism remains elusive. N-terminal Toll/interleukin-1 receptor (TIR) domains are self-sufficient to trigger immune signaling. We showed that the conditional activation of two well-characterized TIR-containing NLRs (TNLs) or their corresponding TIR domains alone induce the same signaling route at permissive temperature (ENHANCED DISEASE SUSCEPTIBLITY 1 [EDS1]/helper NLRs that display an RPW8-like N-terminal CC_R domain [RNL] requirement and activation of the salicylic acid sector) in Arabidopsis. Yet, this signaling pathway is maintained under elevated temperatures (30°C) when induced by TIRs only but not full-length TNLs. This work underlines the need to further study how NLRs are impacted by an increase in temperature, which is particularly important to improve the resilience of plant disease resistance in a warming climate.

2025-02-28·Combinatorial Chemistry & High Throughput Screening

Revealing the Mechanism of Buzhong Yiqi Tang in Ameliorating Autoimmune Thyroiditis via the Toll-like Receptor Pathway

Article

作者: Jin, Zhe ; Gao, Hao ; Liu, Donglin ; Chen, Yiran ; Li, Jiayun ; Yang, Xiao ; Chen, Si ; Wang, Zhimin ; Liu, Ziyu ; Zhao, Zhuo

Objective:Autoimmune thyroiditis (AIT) is one of the most common autoimmune diseases and often causes hypothyroidism in patients. As a traditional formulation in my country, Buzhong Yiqi decoction (BZYQD) has significant effects in improving clinical symptoms of AIT and reducing autoantibody titers, but its specific mechanism of action needs to be further explored. The purpose of this study was to explore the effective targets and related mechanisms of Buzhong Yiqi decoction in AIT mice based on transcriptome sequencing technology.Methods:Forty NOD.H-2h4 mice were selected and 0.05% NaI was drinking ad libitum for 8 weeks to establish AIT mice, and drug intervention was performed according to groups for 8 weeks. The groups were as follows: control group, Model Group, Buzhong Yiqi Decoction group (9.56 g·kg-1) and Positive control group (Se yeast tablets, 3.033×10-5 g·kg-1), of which Buzhong Yiqi Decoction was the clinical equivalent dose. Thyroid tissues of the Model Group, blank group and Buzhong Yiqi Decoction group were subjected to transcriptome sequencing to analyze the expression of differential genes, and enrichment analysis was carried out. Hematoxylin and eosin staining (HE staining) was used to detect the pathological changes in thyroid tissues, and enzymelinked immunosorbent assay (ELISA) was used to detect the content of serum thyroglobulin antibody (TGAb) to determine the intervention effect of Buzhong Yiqi Decoction; Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was performed based on the transcriptome sequencing results to detect the expression of TLR8, JUN, TICAM2, TIRAP, and IL-1β mRNA in thyroid tissue.Results:According to the transcriptome results, compared with the blank group, there were 327 significantly up-regulated genes and 440 significantly down-regulated genes in the Model Group; compared with the Model Group, there were 502 significantly up-regulated genes and 380 significantly down-regulated genes in the Buzhong Yiqi Decoction group, mainly enriched in immune inflammation and other related pathways including Toll-like receptors. Animal experiments showed that compared with the control group, the model group had obvious lymphocyte infiltration in thyroid tissue under light microscope, a significant increase in inflammatory cells, a significant increase in TGAb content in serum, and a significant increase in TLR8, JUN, TICAM2, TIRAP, IL-1β mRNA expression was observed (P<0.05 or P<0.01). Compared with the Model Group, Buzhong Yiqi Decoction could significantly improve the inflammatory damage of thyroid tissue in AIT mice, reduce the content of TGAb in serum, and down-regulate the expression of TLR8, JUN, TICAM2, TIRAP, IL-1β mRNA (P<0.05 or P<0.01).Conclusion:Buzhong Yiqi Decoction can effectively improve the inflammatory damage of AIT, and inhibiting the abnormal activation of the Toll-like receptor pathway may be one of its intervention mechanisms.

项与 TICAM2 相关的新闻（医药）

2023-06-10

·生物谷

老药新用免疫治疗大突破！Nature重磅：朱晶晶团队首次发现激活α2-AR的降压药可诱导强效抗肿瘤免疫应答！

免疫治疗是一种新兴的癌症治疗方法，它能够通过激活或增强人体免疫系统来对抗肿瘤。其主要优点在于其针对性强、持久性高的长期效果。免疫治疗可以针对个体的肿瘤特征进行定制，从而提高治疗效果。与传统治疗相比，免疫治疗具有较低的毒副作用，并且能够产生持久的免疫记忆，有助于预防复发。然而，免疫治疗也存在一些缺点，同很多药物一样，一些患者在接受免疫检查点抑制剂治疗后可能会出现耐药性，这极大地限制了这种治疗方法的使用，因此，解决这一问题变得迫在眉睫。2023年6月7日，比利时布鲁塞尔路德维希癌症研究所朱晶晶团队在《自然》杂志发表论文：Tumour immune rejection triggered by activation of α2-adrenergic receptors，该研究聚焦于α2-肾上腺素受体激动剂在肿瘤免疫治疗中的关键作用机制，在这项研究中，他们首次发现用于治疗高血压的一些分子可能帮助免疫系统更好地靶向癌细胞。 ARs（肾上腺素受体）是一类G蛋白偶联受体。根据其结构、药理学和信号传导机制，它们被分为两种类型（α和β）和几种亚型，这其中，α2-ARs受体，能够通过Gi信号传递途径抑制腺苷酸环化酶的功能，从而减少环磷酸腺苷（cAMP）和蛋白激酶 A（PKA）的激活。但是，在肿瘤微环境中，存在一些免疫抑制机制，它们通过激活腺苷酸环化酶来增加cAMP的水平，从而抑制对抗肿瘤的免疫反应。正如我们上文中讲到的，科学家们正在开发一些相关的药物，用于癌症免疫治疗。因此作者认为，通过抑制腺苷酸环化酶，α2-AR激动剂可能比这些药物更有效，因为它们可以同时阻断多个增加cAMP水平的免疫抑制途径。为了评估α2-AR在癌症进展中的作用，作者首先使用不同的α2-AR激动剂和拮抗剂治疗结肠肿瘤的小鼠。结果观察到肿瘤生长显著减少，并且小鼠的存活率增加（图1）图1：用α2-AR激动剂GBZ、CLD或GFC或α2-AR拮抗剂YHB或PHE治疗小鼠MC38结肠癌1值得一提的是，研究团队还使用了其他的结肠肿瘤模型，在所有这些模型中，都能观察到α2-AR激动剂治疗后肿瘤生长都有类似的抑制效果。进一步，研究人员在接受了α2-AR激动剂治疗的小鼠中观察到，MC38-OVA、TC-1和TiRP肿瘤中的肿瘤浸润淋巴细胞（TILs）上的PD-1表达增加了，同时肿瘤微环境（TME）细胞上的PD-L1也增加了（图2）。图2：CD8+ T细胞中PD-1的表达(上)，MC38-OVA、TC-1和TiRP肿瘤中PD-L1的总活细胞(下)1这引起了科研团队的兴趣，因此作者测试了α2-AR激动剂与免疫检查点抑制剂的联合应用。在MC38-OVA模型中，他们观察到抗PD-1与α2-AR激动剂的联合应用显示出强大的协同抗肿瘤效果，导致大多数小鼠完全没有肿瘤生长（图3）。图3：用GBZ、CLD、ICB或联合治疗小鼠MC38-OVA 的进展情况1接下来，作者将CLD的抗肿瘤效力与普萘洛尔（PRP）-一种β2-AR拮抗剂进行了比较。从实验结果中观察到CLD在CT26癌症模型中比PRP更有效。与PRP相比，α2-AR激动剂的抗肿瘤效力增强，因此符合作者一开始的假设，即通过抑制腺苷酸环化酶产生cAMP，α2-AR激动剂可以阻断多个导致cAMP介导的免疫抑制途径。此外，研究人员还发现，α2-AR激动剂处理后，肿瘤组织中的肿瘤相关巨噬细胞呈现更高水平的活性状态，与更强的抗肿瘤免疫应答密切相关。此外，α2-AR激动剂还促进了CD4+ T细胞的活化和增殖，并增加了产生抗肿瘤免疫应答所需的细胞因子。综上所述，这项研究为开发新的免疫治疗策略和药物提供了全新的思路。通过调节肿瘤相关巨噬细胞和CD4+ T细胞的功能，α2-AR激动剂具备潜在成为免疫治疗药物的特质（图4）。这类激动剂几十年来已经被用于治疗高血压患者，它们的药理学和安全性已经得到了广泛研究。尽管可能需要使用比以往更高的剂量并减轻镇静作用，但是这项发现仍值得在癌症患者中进行α2-肾上腺素受体激动剂的临床测试。研究人员对未来的临床试验抱有极大期待，希望进一步验证这些发现，并将其推广应用于临床实践，为癌症患者带来福音。图4：通过口服途径给予可乐定的抗肿瘤效果（a，b），以及α2-肾上腺素受体激动剂的抗肿瘤活性的示意模型1在面对免疫检查点抑制剂在临床中表现出耐药性这一新的挑战中，全世界的科学家都正在积极努力，探索新的免疫调控机制和药物靶点，以提高癌症治疗的效果。除了本文中提出的这项研究之外，还有一些新的疗法被提出，比如CAR-T细胞疗法，这种疗法利用改造的免疫细胞来针对癌细胞，具有更为精准和个体化的作用方式，有望克服耐药性带来的限制。另一方面，研究人员也在研究免疫抑制机制的调节，以阻止肿瘤对免疫治疗的逃逸机制。这些努力旨在拓宽免疫治疗的应用领域，使更多患者能够受益。参考文献：1. Zhu, J., Naulaerts, S., Boudhan, L. et al. Tumour immune rejection triggered by activation of α2-adrenergic receptors. Nature (2023).撰文 | 之予编辑 | 小白活动推荐精彩推荐：1、BMC Medicine：南医大最新研究发现，低碳水化合物比限制热量饮食减轻体重更有效！2、打破百年误解！Nature最新研究：首次证实大脑整体形状对大脑功能的影响远大于复杂的神经元连接！3、Cell子刊：重大突破！逼迫癌细胞“自杀”的方法找到了！4、“二阳”来袭别大意！BMJ重磅研究：多达18%的感染者在感染两年后仍受到新冠后遗症的影响5、白天睡不够，晚上睡不着？近5万名网民研究显示：睡前1小时玩手机，入睡延迟的可能性大大增加！

免疫疗法

分析

对领域进行一次全面的分析。

或

查看完整样例数据

生物医药百科问答

全新生物医药AI Agent 覆盖科研全链路，让突破性发现快人一步

立即开始免费试用!

智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。

立即开始数据试用!

智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。