更新于：2024-11-01

FCER1A

更新于：2024-11-01

基本信息

别名

Fc epsilon receptor Ia、Fc fragment of IgE receptor Ia、Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide

+ [8]

简介

High-affinity receptor for immunoglobulin epsilon/IgE. Mediates IgE effector functions in myeloid cells. Upon IgE binding and antigen/allergen cross-linking initiates signaling pathways that lead to myeloid cell activation and differentiation. On mast cells, basophils and eosinophils stimulates the secretion of vasoactive amines, lipid mediators and cytokines that contribute to inflammatory response, tissue remodeling and cytotoxicity against microbes. Triggers the immediate hypersensitivity response to allergens as a host defense mechanism against helminth parasites, pathogenic bacteria and venom toxicity. When dysregulated, it can elicit harmful life-threatening allergic and anaphylactic reactions.

关联

项与 FCER1A 相关的药物

Benzylpenicilloyl Polylysine

青霉烯酰聚赖氨酸

靶点

FCER1A

作用机制

FCER1A激动剂

在研机构

AllerQuest LLC

原研机构

AllerQuest LLC

在研适应症

诊断试剂 [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1974-07-25

Lesigercept

靶点

FCER1A

作用机制

FCER1A拮抗剂

在研机构

Yuhan Corp.

原研机构

GI Innovation, Inc.

在研适应症

慢性荨麻疹 [+2]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

FCER1A antagonists-11(Icahn School of Medicine at Mount Sinai)

靶点

FCER1A

作用机制

FCER1A拮抗剂

在研机构

Icahn School of Medicine at Mount Sinai

原研机构

Icahn School of Medicine at Mount Sinai

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 FCER1A 相关的临床试验

NCT06406114 / Not yet recruiting临床2期IIT

Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing

Cephalosporin antibiotics are commonly used but can result in allergic reactions and anaphylaxis. There is no clear diagnostic approach for cephalosporin-allergic patients, and guidance for the use of other antibiotics in allergic patients is based on side chain chemical similarity and limited skin testing evidence. This project includes a clinical trial and mechanistic studies to optimize the approach to cephalosporin allergy and advance future diagnostics.

开始日期2024-08-01

申办/合作机构

The General Hospital Corp.

[+1]

NCT05960708 / Completed临床1期

A Randomized, Double-Blind, Placebo/Active Controlled, Single Dose, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Subcutaneous Injections of YH35324 in Patients With Various Allergic Diseases

This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) following a single subcutaneous injection of YH35324 in subjects with various allergic diseases.

开始日期2023-08-23

申办/合作机构

Yuhan Corp.

NCT05564221 / Active, not recruiting临床1期

A Randomized, Double-Blind, Placebo/Active Controlled, Multiple Ascending Dose, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Subcutaneous Injections of YH35324 in Atopic Healthy Subjects or Subjects With Allergic Diseases

This study aims to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles following multiple subcutaneous injections of YH35324 in healthy subjects or subjects with allergic diseases, who have atopy.

开始日期2022-11-01

申办/合作机构

Yuhan Corp.

100 项与 FCER1A 相关的临床结果

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100 项与 FCER1A 相关的转化医学

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0 项与 FCER1A 相关的专利（医药）

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425

项与 FCER1A 相关的文献（医药）

2024-10-02·Journal of Asthma

Analysis of the potential molecular mechanisms of asthma and gastroesophageal reflux disease

Article

作者: Zhang, Wen ; Jiang, Chenglin ; Chen, Changdan ; Zhang, Wei ; Zheng, Xiujin

OBJECTIVEAsthma and gastroesophageal reflux disease (GERD) often occur simultaneously, with GERD being a comorbidity of asthma. This study aimed to explore the biological markers related to asthma and GERD by bioinformatics analysis.METHODSInitially, gene expression datasets for asthma and GERD were obtained from the Gene Expression Omnibus database, and subsequent differential expression analysis yielded 620 differentially expressed genes (DEGs) for asthma and 2367 DEGs for GERD. The intersection of these two gene sets yielded a total of 84 DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these genes may be involved in steroid hormone secretion and cellular stress response. Five hub genes (PTGDR2, CPA3, FCER1A, TPSAB1, and IL1RL1) were identified by a protein-protein interaction (PPI) network analysis and topological algorithm.RESULTSEnrichment analysis results indicated that hub genes may be involved in hormone secretion and disease development, particularly in regulating the renin-angiotensin system and systemic arterial blood pressure. PTGDR2, CPA3, TPSAB1, and IL1RL1 were upregulated in both asthma and GERD patient groups, while FCER1A was upregulated in asthma patients but downregulated in GERD patients. Through drug prediction, 22 drugs targeting hub genes PTGDR2, FCER1A, and TPSAB1 were identified. By constructing a transcription factor (TF)-target gene network, we found that eight TFs may regulate the expression of PTGDR2, FCER1A, and IL1RL1.CONCLUSIONHence, Asthma and GERD were related to steroid hormone secretion and the renin-angiotensin system.

2024-10-01·Human Genetics

A methodology for gene level omics-WAS integration identifies genes influencing traits associated with cardiovascular risks: the Long Life Family Study

Article

作者: Moghaddam, Vaha Akbary ; Brent, Michael R. ; Anema, Jason A. ; Province, Michael A. ; Liao, Shu ; Wojczynski, Mary K. ; Jung, Wooseok J ; Jung, Wooseok J. ; Acharya, Sandeep ; Kang, Yu S ; Schwander, Karen ; Brent, Michael R ; Wojczynski, Mary K ; Lin, Shiow ; Feitosa, Mary F. ; Connell, Jeff O. ; Connell, Jeff O ; Province, Michael A ; Anema, Jason A ; Feitosa, Mary F ; Kang, Yu S.

AbstractThe Long Life Family Study (LLFS) enrolled 4953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8 × 10–7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein–Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genes FCER1A, MS4A2, GATA2, HDC, and HRH4 in atherosclerosis risks. Our findings also suggest that lower expression of ATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest that ENPP3 may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform (https://nf-co.re/omicsgenetraitassociation).

2024-07-01·Allergy

The effects of inhaled corticosteroids on healthy airways

Article

作者: MacIsaac, Julia L. ; Hinks, Timothy S. C. ; Khalfaoui, Latifa ; Choy, David F. ; Hargadon, Beverley ; Bradding, Peter ; Symon, Fiona A. ; Richardson, Matthew ; Siddiqui, Salman ; Austin, Cary D. ; Marchi, Emanuele ; Mar, Jordan S. ; Clifford, Rachel ; Kobor, Michael S. ; Rajasekar, Poojitha ; Arron, Joseph R.

AbstractBackgroundThe effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined.ObjectivesTo delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease‐related genes and disease‐related alterations in ICS responsiveness.MethodsRandomized open‐label bronchoscopy study of high‐dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics.ResultsICS induced small between‐group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type‐2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell‐mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA‐DQB2, CD96, PTPN7), B‐cell immunity (CD20, immunoglobulin heavy and light chains) and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL‐17‐dependent gene signature was not upregulated by ICS.ConclusionsIn healthy airways, 4‐week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type‐2 inflammation. This implies that homeostasis in health involves tonic type‐2 signalling in the airway mucosa, which is exquisitely sensitive to ICS.

项与 FCER1A 相关的新闻（医药）

2023-12-23

·生物制药小编

TRM-TAM来源与分化的差异性：人vs小鼠

组织驻留巨噬细胞(TRM)在免疫和组织修复中具有独特的转录特征和功能，同时也是小鼠和人体肿瘤相关巨噬细胞(TAM)的重要来源。然而人和小鼠中的巨噬细胞分子生物学描述并不相同。TRM异质性对TAM的影响在肺癌、胰腺癌和乳腺癌的小鼠模型中，组织驻留巨噬细胞来源的肿瘤相关巨噬细胞(TRM-TAMs)积极支持早期肿瘤扩散并促进肿瘤生长。TRM-TAM在不同的癌症中表现出不同的功能特性。例如，胰腺中的TRM-TAM表现出独特的促纤维化表型，产生和重塑细胞外基质分子；肺TRM-TAM则通过诱导肿瘤细胞上皮-间充质转化和突出的Treg细胞诱导来减弱抗肿瘤适应性免疫反应，从而促进肿瘤侵袭；TIM4+胸/腹膜腔驻留巨噬细胞通过将CD8+ T细胞隔离在远离肿瘤靶点的部位上来损害抗肿瘤免疫。一组可自我更新的CD163+ TIM4+ 组织驻留网膜巨噬细胞通过为肿瘤干细胞提供保护性生态位，与卵巢癌细胞的转移扩散有因果关系，等等。而在TAMs研究中发现，TAM的不同来源(比如TRM来源和单核细胞来源)可能导致其对耗竭或调节干预表现出不同的敏感性，在治疗中或许就需要双重TAM靶向策略以提高免疫治疗效果。同时，人和小鼠中不同表征的巨噬细胞分化阶段的比例在两个物种之间有很大的差异，也会影响对于临床疗效的判断。cavity macrophages：人vs鼠组织驻留的网膜腔巨噬细胞是TAM的重要来源之一，在卵巢癌、肝纤维化等实体瘤TME的形成中起到重要作用。大多数小鼠网膜巨噬细胞特征是GATA6+和CXCL1、SELP等其他相关基因的表达。体内动态平衡中，小鼠腹膜巨噬细胞存在两种不同的巨噬细胞群。（一）大腹腔巨噬细胞(LCM)LCM是更主要的巨噬细胞群，仅存在于腹膜、胸膜和心包腔的腔液中。表征：LCM表达F4/80hi CD115+ ICAM2+，来源于胚胎前体，依赖转录因子GATA6进行发育和维持。在没有GATA6的情况下，LCM会下调CD73，并上调CD206和LYVE1等。功能：作为对炎症或损伤的反应，LCM通过聚集在扰动的空洞表面或纤维蛋白凝块内来帮助遏制早期感染发生。（二）小腹腔巨噬细胞(SCM)表征：SCM表达F4/80lo MHCII+，超过75%的SCM还表达CD226。该亚群起源于类似于单核细胞的CCR2依赖性前体，其发育程序依赖于转录因子IRF4。功能：以前一般将其归类为M1类巨噬细胞。但是其中部分群体的同时表达巨噬细胞和DC的混合功能特征。LCM和SCM都表达CD115和和CD11b。在人体中：尽管人体中同样存在GATA6+的腹膜巨噬细胞，但是数量非常少。相对地，人体中数量丰富的CCR2+或GLUL+巨噬细胞则没有在小鼠中发现明显对应的亚群。CCR2+也代表了与单核细胞浸润有关的早期分化阶段。若要对应，人体表达GATA6+的巨噬细胞亚群为TIMD4+亚群，和小鼠中的GATA6+ LCM1亚群一样表达SELP信使RNA。而表达相同RNA的其他巨噬细胞还包括：MRC1+ LYVE1+ CD163+ 巨噬细胞；GLUL+ CD163++ FABP5+ 巨噬细胞；Marco+ 巨噬细胞；IL1B+ 巨噬细胞；干扰素刺激基因(ISG)+ 巨噬细胞；CCR2+ 巨噬细胞；以及CD1C+CD14+ 巨噬细胞。其中，小鼠中存在和MRC1+LYVE1+CD163+ 巨噬细胞同样表达和起源的亚群，但是比例比人体内更少。这代表着人腹腔巨噬细胞的分化周期相对于小鼠来说，更多存在于GATA6表达之前的分化阶段，许多巨噬细胞似乎在GATA6表达之前的阶段停滞或在表达后不久死亡。而CD1C+CD14+ 巨噬细胞则和小鼠F4/80lo MHCII+ SCM具有相似的特征。人CD1C+ 细胞在小鼠中可对应CD226+ 干细胞。在人体中，CD1C+细胞相对丰富，可分为：CD1C+ CD14+亚群：表达编码CD16、CD115、CD63、CD163和巨噬细胞相关基因；CD1C+ CD14- 亚群：表达一些DC经典表征基因，包括LTB、肥大细胞特异性表征FCER1A、CD37和CD1E。同时，CD1c+人腹膜单核巨噬细胞群中同样存在具有混合巨噬细胞和DC特征的CD1c+ cDC2和CD1c+ CD14+ CD64+ CD226+ 细胞亚群。小结巨噬细胞的亚群表征多样，在人体中的研究也尚待继续完善。F4/80、Ly6G和Ly6C等小鼠特异性分子标记物在人巨噬细胞中不表达，为研究中在小鼠模型和人体之间进行翻译带来了困难。更准确的亚群特征对应研究或提高TME相关免疫疗法的可行性。参考文献：1.Han, J., Gallerand, A., Erlich, E.C. et al. Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species. Nat Immunol (2023). https://doi.org/10.1038/s41590-023-01688-72.Andrea Vogel, Thomas Weichhart,Tissue-resident macrophages — early passengers or drivers in the tumor niche?,Current Opinion in Biotechnology,Volume 83,2023,102984,ISSN 0958-1669,https://doi.org/10.1016/j.copbio.2023.102984.3.Zhi Wang, Kailei Du, Nake Jin, Biao Tang, Wenwu Zhang,Macrophage in liver Fibrosis: Identities and mechanisms,International Immunopharmacology,Volume 120,2023,110357,ISSN 1567-5769,https://doi.org/10.1016/j.intimp.2023.110357.

免疫疗法