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Decoding IgE Fc receptors

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Abstract

Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases by interacting with two membrane receptors: high-affinity FcεRI and low-affinity FcεRII (CD23). Allergen-induced IgE-occupied EcεRI aggregation on the mast cell or basophil cell surface leads to the activation of intracellular signaling events and eventually the release of pre-formed and de novo synthesized inflammatory mediators. The role of FcεRII in allergic diseases has been proposed to include regulation of IgE synthesis, enhanced histamine release from basophils, and a contribution to Ag-IgE complex presentation but the exact function of CD23 remains poorly understood. This review summarizes some new developments in IgE Fc-receptor studies with an emphasis on regulation of FcεRI expression and signal transduction, including monomeric IgE, lipid raft segregation, and some recently identified negative regulators. A better understanding of signaling events following IGE FcR aggregation will shed new light on how allergy patients might be treated more safely and effectively.

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References

  1. Daeron M: Fc receptor biology. Ann Rev Immunol 1997; 15:2203–234.

    Article  Google Scholar 

  2. Nadler MJ, Matthews SA, Turner H, Kinet JP: Signal transduction by the high-affinity immunoglobulin E receptor FcεRI: coupling form to function. Adv Immunol 2001; 76:325–355.

    Article  Google Scholar 

  3. Parravicini V, Gadina M, et al: Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol 2002; 3: 741–748.

    PubMed  CAS  Google Scholar 

  4. Galli SJ, Kalesinikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M: Mast cells as “tunable” effectors and immunoregulatory cells: recent advances. Annu Rev Immunol 2005; 23:749–786.

    Article  PubMed  CAS  Google Scholar 

  5. Novak N, Kraft S, Bieber T: IgE receptors Curr Opin Immunol 2001; 13:721–726.

    Article  PubMed  CAS  Google Scholar 

  6. Mukai K, Matsuoka K, Taya C, et al: Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity 2005; 23:191–202.

    Article  PubMed  CAS  Google Scholar 

  7. Schroeder JT, Bieneman AP, Xiao H, et al: TLR9- and Fcepsilon RI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. J Immunol 2005; 175:5724–5731.

    PubMed  CAS  Google Scholar 

  8. Gounni AS, Wellemans V, Yang J, et al: Human airway smooth muscle cells express the high affinity receptor for IgE (Fc epsilon RI): a critical role of Fc epsilon RI in human airway smooth muscle cell function. J Immunol 2005; 175: 2613–2621.

    PubMed  CAS  Google Scholar 

  9. Donnadieu E, Jouvin MH, Rama S, et al: Competing functions encoded in the allrgy-associated F(c)epsilon-RIbeta gene. Immunity 2003; 18:665–674.

    Article  PubMed  CAS  Google Scholar 

  10. Fiebiger E, Tortorella D, Jouvin MH, Kinet JP, Ploegh HL: Cotranslational endoplasmic reticulum assembly of Fc{varepsilon}RI controls the formation of functional IgE-binding receptors. J Exp Med 2005;201:267–277.

    Article  PubMed  CAS  Google Scholar 

  11. Nishiyama C, Akizawa Y, Nishiyama M et al: Poly-morphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy. J Immunol 2004; 173: 6458–6464.

    PubMed  CAS  Google Scholar 

  12. Hasegawa M, Nishiyama C, Nishiyama M, et al: A novel −66T/C polymorphism in Fc epsilon RI alpha-chain promoter affecting the transcription activity: possible relationship to allergic diseases. J Immunol 2003; 171:1927–1933.

    PubMed  CAS  Google Scholar 

  13. Bobrzynski T, Fux M, Vogel M, Stadler MB, Stadler BM, Miescher SM: A high-affinity natural autoantibody from human cord blood defines a physiologically relevant epitope on the FcepsilonRIalpha. J Immunol 2005; 175:6589–6596.

    PubMed  CAS  Google Scholar 

  14. Bruhus P, Fremont S, Daeron M: Regulation of allergy by Fc receptors. Curr Opin Immunol 2005; 17:662–669.

    Article  CAS  Google Scholar 

  15. Kawakami T, Galli SJ: Regulation of mast-cell and basophile function and survival by IgE. Nat Rev Immunol 2002; 10:773–786.

    Article  CAS  Google Scholar 

  16. Kitaura J, Xiao W, Maeda-Yamamoto M, Kawakami Y, Lowell CA, Kawakami T: Early divergence of Fc epsilon receptor I signals for receptor up-regulation and internalization from degranulation, cytokine production, and survival. J Immunol 2004; 173;4317–4323.

    PubMed  CAS  Google Scholar 

  17. Lam V, Kalesnikoff J, Lee CW, et al IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE + antigen but distinct from those used by Steel factor. Blood 2003; 102:1405–1413.

    Article  PubMed  CAS  Google Scholar 

  18. Kitaura J, Kinoshita T, Matsumoto M, et al: IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion. Blood 2005; 105:322–3229.

    Article  CAS  Google Scholar 

  19. Kitaura J, Song J, Tsai M, et al: Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI. Proc Natl Acad Sci USA 2003; 100: 12911–12916.

    Article  PubMed  CAS  Google Scholar 

  20. James LC, Roversi P, Tawfik DS: Antibody multispecificity mediated by conformational diversity. Science 2003; 299:1362–1367.

    Article  PubMed  CAS  Google Scholar 

  21. Schweitzer-Stenner R, Pecht I: Death of a dogma or enforcing the artificial: monomeric IgE binding may initiate mast cell response by inducing its receptor aggregation. J Immunol 2005; 174;4461–4464.

    PubMed  CAS  Google Scholar 

  22. Holowka D, Gosse JA, Hammond AT, et al: Lipid segregation and IgE receptor signaling: a decade of progress. Biochim Biophys Acta 2005; 1746:252–259.

    Article  PubMed  CAS  Google Scholar 

  23. Young RM, Zheng X, Holowka D, Baird B: Reconstitution of regulated phosphorylation of FcepsilonRI by a lipid raft-excluded protein-tyrosine phosphatase. J Biol Chem 2005; 280:1230–1235.

    Article  PubMed  CAS  Google Scholar 

  24. Gosse JA, Wagenknecht-Wiesner A, Holowka D, Baird B: Transmembrane sequences are determinants of immunoreceptor signaling. J Immunol 2005; 175: 2123–2131.

    PubMed  CAS  Google Scholar 

  25. Wu M, Holowka D, Craighead HG, Baird B: Visualization of plasma membrane compartmentalization with patterned lipid bilayers. Proc Natl Acad Sci USA 2004; 101:13798–13803.

    Article  PubMed  CAS  Google Scholar 

  26. Lesourne R, Fridman WH, Daeron M: Dynamic interactions of Fc gamma receptor HB with filamin-bound SHIPI amplify filamentous actin-dependent negative regulation of Fc epsilon receptor I signaling. J Immunol 2005; 174:1365–1373.

    PubMed  CAS  Google Scholar 

  27. Larson DR, Gosse JA, Holowka DA, Baird BA, Webb WW: Temporally resolved interactions between antigen-stimulated IgE receptors and Lyn kinase on living cells. J Cell Biol 2005; 171:527–536.

    Article  PubMed  CAS  Google Scholar 

  28. Gimborn K, Lessmann E, Kuppig S, Krystal G, Huber M: SHIP down-regulates Fcepsilon R1-induced degranulation at supraoptimal IgE or antigen levels. J Immunol 2005; 174:507–516.

    PubMed  CAS  Google Scholar 

  29. Xiao W, Nishimoto H, Hong H, et al: Positive and negative regulation of mast cell activation by Lyn via the Fcepsilon RI. J Immunol 2005; 175:6885–6892.

    PubMed  CAS  Google Scholar 

  30. Furumoto Y, Nunomura S, Terada T, Rivera J, Ra C: The EcepsilonRIbeta immunoreceptor tyrosine-based activation motif exerts inhibitory control on MAPK and IkappaB kinase phosphorylation and mast cell cytokine production. J Biol Chem 2004; 279:49177–49187.

    Article  PubMed  CAS  Google Scholar 

  31. Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM: Lyn tyrosine kinase: accentuating the positive and the negative. Immunity 2005; 22:9–18.

    PubMed  Google Scholar 

  32. Hernandez-Hansen V, Smith AJ, Surviladze Z, et al: Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. J Immunol 2004; 173:100–112.

    PubMed  CAS  Google Scholar 

  33. Odom Gomez G, Kovarova M, et al: Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase. J Exp Med 2004; 199:1491–1502.

    Article  PubMed  CAS  Google Scholar 

  34. Simon M, Vanes L, Geahlen RL, Tybulewicz VL: Distinct roles for the linker region tyrosines of Syk in FcepsilonRI signaling in primary mast cells. J Biol Chem 2005; 280:4510–4517.

    Article  PubMed  CAS  Google Scholar 

  35. Kettner A, Kumar L, Anton IM, et al: WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells. J. Exp Med 2004; 199:357–368.

    Article  PubMed  CAS  Google Scholar 

  36. Pasquier B, Launay P, Kanamaru Y, et al: Identification of FcalphaRI as an inhibitory receptor that controls inflammation: dual role of FcRgamma ITAM. Immunity 2005; 22:31–42.

    PubMed  CAS  Google Scholar 

  37. Tam SY, Tsai M, Snouwaert JN, et al: RabGEF1 is a negative regulator of mast cell activation and skin inflammation. Nat Immunol 2004; 5:844–852.

    Article  PubMed  CAS  Google Scholar 

  38. D'Amato G: Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory disease. Eur J Pharmacol 2006; 533: 302–307.

    Article  PubMed  CAS  Google Scholar 

  39. Bousquet J, Cabrera P, Berkman N, et al: The effect of treatment with omalizumab an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy 2005; 60:302–308.

    Article  PubMed  CAS  Google Scholar 

  40. Zhu D, Kepley CL, Zhang M, Zhang K, Saxon A: A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein inhibits Fc epislon RI-mediated degranulation. Nat Med 2002; 8:518–521.

    Article  PubMed  CAS  Google Scholar 

  41. Tam SW, Demissie S, Thomas D, Daeron M. A bispecific antibody against human IgE and human FcgammaRII that inhibits antigen-induced histamine release by human mast cells and basophils. Allergy 2004; 59: 772–780.

    Article  PubMed  CAS  Google Scholar 

  42. Hibbert RG, Teriete P, Grundy GJ, et al: The structure of human CD23 and its interactions with IgE and CD21. J Exp Med 2005; 202:751–760.

    Article  PubMed  CAS  Google Scholar 

  43. Puccetti A, Bason C, Simeoni S, et al: In chronic idiopathic urticaria autoantibodies against Fc epsilonRII/CD23 induce histamine release via eosinophil activation. Clin Exp Allergy 2005; 35:1599–1607.

    Article  PubMed  CAS  Google Scholar 

  44. Getahun A, Hjelm F, Heyman B: IgE enhances antibody and T cell responses in vivo via CD23+ B cells. J Immunol 2005; 175:1473–1482.

    PubMed  CAS  Google Scholar 

  45. Poole JA, Meng J, Reff M, Spellman MC, Rosenwasser LJ: Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects. J Allergy Clin Immunol 2005; 116:780–788.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE 68178

    Ming Zhang & Devendra K. Agrawal PhD (Professor of Biomedical Science, Medicine and Medical Microbiology and Immunology)

  2. Department of Biomedical Sciences, Creighton University of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE 68178

    Richard F. Murphy & Devendra K. Agrawal PhD (Professor of Biomedical Science, Medicine and Medical Microbiology and Immunology)

  3. Department of International Medicine, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE 68178

    Devendra K. Agrawal PhD (Professor of Biomedical Science, Medicine and Medical Microbiology and Immunology)

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  1. Ming Zhang
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  3. Devendra K. Agrawal PhD
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Correspondence to Devendra K. Agrawal PhD.

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Zhang, M., Murphy, R.F. & Agrawal, D.K. Decoding IgE Fc receptors. Immunol Res 37, 1–16 (2007). https://doi.org/10.1007/BF02686092

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