Fc epsilon receptors: Introduction

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The FcεRI is a tetrameric complex that binds the Fc domain of the ε heavy chain of immunoglobulin E (IgE). It consists of one α subunit that binds antibody, one β subunit that is a signal transducer/amplifier [1,7], and two γ subunits that initiate signalling [5]. This complex can be annotated as αβγ2. FcεRI is constitutively expressed on mast cells and basophils and is inducible on eosinophils [8,10] and plays a central role in regulating the allergic response [9,13]. IgE-antigen complex signalling through αβγ2 activates the cells expressing the receptor, inducing mast cell and basophil degranulation and release of preformed inflammatory mediators [12]. Eosinophilic FcεRI is involved in defence against parasites [3]. In antigen presenting cells FcεRIα-γ2 (a trimeric complex with no signal amplifying β subunit) facilitates a role in antigen presentation [12]. The FcεRI-IgE pathway is an important drug target in asthma therapeutic development, with the first anti-IgE monoclonal antibody for asthma (omalizumab) being approved in 2003. IgG autoantibodies against FcεRI and IgE have been detected in a proportion of cases of chronic urticaria, suggesting an autoimmune pathology, and thereby implicating the Fcε receptor-IgE axis in autoimmune disease [2,4,6,11]. Further details of FcεRI signalling and function are provided on the Reactome pathway database Fc epsilon receptor (FCERI) signaling page.

A second identified receptor for IgE, FcεRII (CD23) is a low affinity receptor with no structural similarities to other Fc receptors. This second receptor is expressed on B cells and is involved in the regulation of IgE production [14].

References

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1. Dombrowicz D, Lin S, Flamand V, Brini AT, Koller BH, Kinet JP. (1998) Allergy-associated FcRbeta is a molecular amplifier of IgE- and IgG-mediated in vivo responses. Immunity8 (4): 517-29. [PMID:9586641]

2. Fiebiger E, Maurer D, Holub H, Reininger B, Hartmann G, Woisetschläger M, Kinet JP, Stingl G. (1995) Serum IgG autoantibodies directed against the alpha chain of Fc epsilon RI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients?. J. Clin. Invest.96 (6): 2606-12. [PMID:8675625]

3. Gounni AS, Lamkhioued B, Ochiai K, Tanaka Y, Delaporte E, Capron A, Kinet JP, Capron M. (1994) High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature367 (6459): 183-6. [PMID:8114916]

4. Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. (1993) Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N. Engl. J. Med.328 (22): 1599-604. [PMID:7683772]

5. Kinet JP. (1999) The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu. Rev. Immunol.17: 931-72. [PMID:10358778]

6. Li X, Kimberly RP. (2014) Targeting the Fc receptor in autoimmune disease. Expert Opin. Ther. Targets18 (3): 335-50. [PMID:24521454]

7. Lin S, Cicala C, Scharenberg AM, Kinet JP. (1996) The Fc(epsilon)RIbeta subunit functions as an amplifier of Fc(epsilon)RIgamma-mediated cell activation signals. Cell85 (7): 985-95. [PMID:8674126]

8. Ochiai K, Wang B, Rieger A, Kilgus O, Maurer D, Födinger D, Kinet JP, 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. [PMID:8156009]

9. Okayama Y, Kashiwakura JI, Matsuda A, Sasaki-Sakamoto T, Nunomura S, Yokoi N, Ebihara N, Kuroda K, Ohmori K, Saito H et al.. (2012) The interaction between Lyn and FcεRIβ is indispensable for FcεRI-mediated human mast cell activation. Allergy67 (10): 1241-9. [PMID:22845063]

10. Prussin C, Metcalfe DD. (2006) 5. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol.117 (2 Suppl Mini-Primer): S450-6. [PMID:16455345]

11. Tong LJ, Balakrishnan G, Kochan JP, Kinét JP, Kaplan AP. (1997) Assessment of autoimmunity in patients with chronic urticaria. J. Allergy Clin. Immunol.99 (4): 461-5. [PMID:9111489]

12. Turner H, Kinet JP. (1999) Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature402 (6760 Suppl): B24-30. [PMID:10586892]

13. von Bubnoff D, Novak N, Kraft S, Bieber T. (2003) The central role of FcepsilonRI in allergy. Clin. Exp. Dermatol.28 (2): 184-7. [PMID:12653710]

14. Yokota A, Kikutani H, Tanaka T, Sato R, Barsumian EL, Suemura M, Kishimoto T. (1988) Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): tissue-specific and IL-4-specific regulation of gene expression. Cell55 (4): 611-8. [PMID:2972386]

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To cite this family introduction, please use the following:

Fc epsilon receptors, introduction. Last modified on 02/05/2017. Accessed on 23/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=946.