関: Fc epsilon RII、IgE receptor

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the 18th letter of the Roman alphabet (同)r
the 5th letter of the Greek alphabet
the 6th letter of the Roman alphabet (同)f

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resistance / 17歳以下父兄同伴映画の表示 / rook
エプシロン(ギリシア語アルファベットの第5字E,ε;英語のE,eに相当)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/20 18:54:26」(JST)

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The structure of the FcεRI receptor

Summary of IgE/FcεRI receptor mediated downward signal cascade

The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-affinity receptor for the Fc region of immunoglobulin E (IgE), an antibody isotype involved in the allergy disorder and parasites immunity. FcεRI is a tetrameric receptor complex consisting of one alpha (FcεRIα - antibody binding site), one beta (FcεRIβ - which amplifies the downstream signal), and two disulfide bridge connected gamma chains (FcεRIγ - the site where the downstream signal initiates). It is constitutively expressed on mast cells and basophils^[1] and is inducible in eosinophils.

Tissue distribution

FcεRI is found on epidermal Langerhans cells, eosinophils, mast cells, and basophils.^[2]^[3] As a result of its cellular distribution, this receptor plays a major role in controlling allergic responses. FcεRI is also expressed on antigen-presenting cells, and controls the production of important immune mediators (cytokines, interleukins, leukotrienes, and prostaglandins) that promote inflammation.^[4] The most famous mediator is histamine, which results in the five symptoms of inflammation: heat, swelling, pain, redness and itchiness.

Mechanism of action

Crosslinking of the FcεRI via IgE-antigen complexes leads to degranulation of mast cells or basophils and release of inflammatory mediators.^[5] Under laboratory conditions, degranulation of isolated basophils can also be induced with antibodies to the FcεRIα, which crosslink the receptor. Such crosslinking and potentially pathogenic autoantibodies to the FcεRIα have been isolated from human cord blood, which suggest that they occur naturally and are present already at birth. However, their epitope on FcεRIα was masked by IgE, and the affinity of the corresponding autoantibodies found in healthy adults appeared lowered.^[6]

References

^ Pawankar R (February 2001). "Mast cells as orchestrators of the allergic reaction: the IgE-IgE receptor mast cell network". Curr Opin Allergy Clin Immunol 1 (1): 3–6. doi:10.1097/00130832-200102000-00002. PMID 11964662.
^ Ochiai K, Wang B, Rieger A, Kilgus O, Maurer D, Födinger D, Kinet J, Stingl G, Tomioka H (1994). "A review on Fc epsilon RI on human epidermal Langerhans cells". Int Arch Allergy Immunol. 104. Suppl 1 (1): 63–4. doi:10.1159/000236756. PMID 8156009.
^ Prussin C, Metcalfe D (2006). "5. IgE, mast cells, basophils, and eosinophils". J Allergy Clin Immunol 117 (2 Suppl Mini-Primer): S450–6. doi:10.1016/j.jaci.2005.11.016. PMID 16455345.
^ von Bubnoff D, Novak N, Kraft S, Bieber T (2003). "The central role of FcepsilonRI in allergy". Clin Exp Dermatol 28 (2): 184–7. doi:10.1046/j.1365-2230.2003.01209.x. PMID 12653710.
^ Siraganian RP (December 2003). "Mast cell signal transduction from the high-affinity IgE receptor". Curr. Opin. Immunol. 15 (6): 639–46. doi:10.1016/j.coi.2003.09.010. PMID 14630197.
^ Bobrzynski T, Fux M, Vogel M, Stadler MB, Stadler BM, Miescher SM (November 2005). "A high-affinity natural autoantibody from human cord blood defines a physiologically relevant epitope on the FcepsilonRIalpha". J. Immunol. 175 (10): 6589–96. doi:10.4049/jimmunol.175.10.6589. PMID 16272313.

External links

Fc epsilon RI at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 肥満細胞：表面受容体とシグナル伝達 mast cells surface receptors and signal transduction
2. 肥満細胞由来のメディエーター mast cell derived mediators
3. アナフィラキシーの病態生理 pathophysiology of anaphylaxis
4. IgEの生物学 the biology of ige
5. 食物アレルギーに対する今後の治療法 future therapies for food allergy

English Journal

A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma.

Cohen ES1, Dobson CL1, Käck H2, Wang B3, Sims DA4, Lloyd CO1, England E1, Rees DG1, Guo H2, Karagiannis SN5, O'Brien S1, Persdotter S2, Ekdahl H6, Butler R1, Keyes F1, Oakley S1, Carlsson M2, Briend E1, Wilkinson T1, Anderson IK7, Monk PD8, von Wachenfeldt K9, Eriksson PO10, Gould HJ11, Vaughan TJ1, May RD1.Author information 1MedImmune Ltd; Cambridge, UK.22 AstraZeneca R&D; Mölndal, Sweden.3MedImmune LLC; Hayward, CA USA.4MedImmune PLC; Gaithersburg, MD USA.55 Cutaneous Medicine and Immunotherapy Unit; St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; King's College London School of Medicine & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London; Guy's Hospital; King's College London; London, UK.6Labjoy; Lund, Sweeden.7Johnson & Johnson Innovation; London, UK.8Synairgen Research Ltd; Southampton General Hospital; Southampton, UK.99 Truly Translational Sweden AB; Lund, Sweden.10Spago Imaging AB; Lund, Sweden.11Randall Division of Cell and Molecular Biophysics; Division of Asthma, Allergy and Lung Biology; MRC and Asthma UK Centre for Allergic Mechanisms of Asthma; King's College London; London, UK.AbstractThe critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients in whom IgE neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total IgE levels or body mass. In this study, we sought to generate a novel high affinity anti-IgE antibody (MEDI4212) with potential to treat a broad severe asthma patient population. Analysis of body mass, total and allergen-specific IgE levels in a cohort of severe asthmatics was used to support the rationale for development of a high affinity IgE-targeted antibody therapeutic. Phage display technology was used to generate a human IgG1 lead antibody, MEDI4212, which was characterized in vitro using binding, signaling and functional assay systems. Protein crystallography was used to determine the details of the interaction between MEDI4212 and IgE. MEDI4212 bound human IgE with an affinity of 1.95 pM and was shown to target critical residues in the IgE Cε3 domain critical for interaction with FcεRI. MEDI4212 potently inhibited responses through FcεRI and also prevented the binding of IgE to CD23. When used ex vivo at identical concentration, MEDI4212 depleted free-IgE from human sera to levels ~1 log lower than omalizumab. Our results thus indicate that MEDI4212 is a novel, high affinity antibody that binds specifically to IgE and prevents IgE binding to its receptors. MEDI4212 effectively depleted free-IgE from human sera ex vivo to a level (1 IU/mL) anticipated to provide optimal IgE suppression in severe asthma patients.
mAbs.MAbs.2014 May 1;6(3):755-63. doi: 10.4161/mabs.28394. Epub 2014 Feb 28.
The critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients in whom IgE neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total IgE levels or body mass. In th
PMID 24583620

Allergic sensitization: host-immune factors.

van Ree R1, Hummelshøj L, Plantinga M, Poulsen LK, Swindle E.Author information 1Departments of Experimental Immunology and Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room K0-130, 1105 AZ, Amsterdam, The Netherlands. r.vanree@amc.uva.nl.AbstractAllergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased permeability of the epithelium, which is more susceptible to environmental triggers. Allergens and co-factors from the environment interact with innate immune receptors, such as Toll-like and protease-activated receptors on epithelial cells, stimulating them to produce cytokines that drive T-helper 2-like adaptive immunity in allergy-prone individuals. In this milieu, the next cells interacting with allergens are the dendritic cells lying just underneath the epithelium: plasmacytoid DCs, two types of conventional DCs (CD11b + and CD11b-), and monocyte-derived DCs. It is now becoming clear that CD11b+, cDCs, and moDCs are the inflammatory DCs that instruct naïve T cells to become Th2 cells. The simple paradigm of non-overlapping stable Th1 and Th2 subsets of T-helper cells is now rapidly being replaced by that of a more complex spectrum of different Th cells that together drive or control different aspects of allergic inflammation and display more plasticity in their cytokine profiles. At present, these include Th9, Th17, Th22, and Treg, in addition to Th1 and Th2. The spectrum of co-stimulatory signals coming from DCs determines which subset-characteristics will dominate. When IL-4 and/or IL-13 play a dominant role, B cells switch to IgE-production, a process that is more effective at young age. IgE-producing plasma cells have been shown to be long-lived, hiding in the bone-marrow or inflammatory tissues where they cannot easily be targeted by therapeutic intervention. Allergic sensitization is a complex interplay between the allergen in its environmental context and the tendency of the host's innate and adaptive immune cells to be skewed towards allergic inflammation. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute.
Clinical and translational allergy.Clin Transl Allergy.2014 Apr 15;4(1):12. doi: 10.1186/2045-7022-4-12.
Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased perme
PMID 24735802

Treating severe allergic asthma with anti-IgE monoclonal antibody (omalizumab): a review.

D Amato G, Stanziola A, Sanduzzi A, Liccardi G, Salzillo A, Vitale C, Molino A, Vatrella A, D Amato M.AbstractIncreased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs.Several cases of asthma are atopic in nature, with the trigger for acute asthma attacks and chronic worsening of inflammation being allergens inducing an immune, IgE mediated response.Anti-inflammatory treatments are effective for most of asthma patients, but there are subjects whose disease is incompletely controlled by inhaled or systemic corticosteroids and these patients account for about 50% of the healthcare costs of asthma.Omalizumab is a biological engineered, humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases and with clear efficacy in adolescent and adult patients with severe allergic asthma. The anti-IgE antibody inhibits IgE functions blocking free serum IgE and inhibiting their binding to cellular receptors. By reducing serum IgE levels and IgE receptor expression on inflammatory cells in the context of allergic cascade, omalizumab has demonstrated to be a very useful treatment of atopic asthma, improving quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. Several trials have demonstrated that this therapy is well tolerated and significantly improves symptoms and disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids.
Multidisciplinary respiratory medicine.Multidiscip Respir Med.2014 Apr 15;9(1):23. [Epub ahead of print]
Increased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs.Several cases of asthma are atopic in nature, with the trigger for acute asthma attacks and chronic worsening of inflammation being allergens inducing an immune, I
PMID 24735949

Japanese Journal

Development of Assay for Determining Free IgE Levels in Serum from Patients Treated with Omalizumab

Allergology International 63(Supplement.1), S37-S47, 2014
NAID 130004477231

マスト細胞依存的なアレルギー応答におけるアダプター分子Gab2の役割

YAKUGAKU ZASSHI 133(4), 413-418, 2013
NAID 130003361932

Anti-Allergic Properties of a Matured Fruit Extract of the Date Palm Tree (Phoenix dactylifera L.) in Mite-Sensitized Mice

JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 58(4), 272-277, 2012-08
NAID 120005348472

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★リンクテーブル★

リンク元	「IgE receptor」
拡張検索	「Fc epsilon RII」
関連記事	「RI」「R」「Fc」「F」「epsilon」

「IgE receptor」

high affinity IgE receptor; gamma
Identifiers
Symbol	FCER1G
Alt. symbols	FcεRIγ
Entrez	2207
HUGO	3611
OMIM	147139
RefSeq	NM_004106
UniProt	P30273
Other data
Locus	Chr. 1 q23

high affinity IgE receptor; beta
Identifiers
Symbol	MS4A2
Alt. symbols	FcεRIβ, FCER1B, IGER, APY
Entrez	2206
HUGO	7316
OMIM	147138
RefSeq	NM_000139
UniProt	Q01362
Other data
Locus	Chr. 1 q23

high-affinity IgE receptor; alpha
Identifiers
Symbol	FCER1A
Alt. symbols	FcεRIα, FCE1A
Entrez	2205
HUGO	3609
OMIM	147140
RefSeq	NM_002001
UniProt	P12319
Other data
Locus	Chr. 1 q23