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01.01.2021 | Basic and Applied Science (I Lewkowich, Section Editor) | Ausgabe 1/2021

Mast Cell-Specific MRGPRX2: a Key Modulator of Neuro-Immune Interaction in Allergic Diseases

Zeitschrift:: Current Allergy and Asthma Reports > Ausgabe 1/2021

Autoren:: Monica Thapaliya, Chalatip Chompunud Na Ayudhya, Aetas Amponnawarat, Saptarshi Roy, Hydar Ali

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Wichtige Hinweise

This article is part of the Topical Collection on Basic and Applied Science

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Purpose of Review

Atopic dermatitis (AD) and allergic asthma are complex disorders with significant public health burden. This review provides an overview of the recent developments on Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse counterpart MrgprB2) as a potential candidate to target neuro-immune interaction in AD and allergic asthma.

Recent Findings

Domestic allergens directly activate sensory neurons to release substance P (SP), which induces mast cell degranulation via MrgprB2 and drives type 2 skin inflammation in AD. MRGPRX2 expression is upregulated in human lung mast cells and serum of asthmatic patients. Both SP and hemokinin-1 (HK-1 generated from macrophages, bronchial cells, and mast cells) cause degranulation of human mast cells via MRGPRX2.

Summary

MrgprB2 contributes to mast cell-nerve interaction in the pathogenesis of AD. Furthermore, asthma severity is associated with increased MRGPRX2 expression in mast cells. Thus, MRGPRX2 could serve as a novel target for modulating AD and asthma.

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National Center for Health Statistics. FastStats - Allergies and Hay Fever [Internet]. 2019. Available from: https://www.cdc.gov/nchs/fastats/allergies.htm. Accessed 8 May 2020.

American College of Allergy, Asthma & Immunology. Allergy Facts | ACAAI Public Website [Internet]. 2015. Available from: https://acaai.org/news/facts-statistics/allergies. Accessed 10 May 2020.

da Silva EZM, Jamur MC, Oliver C. Mast cell function: a new vision of an old cell. J Histochem Cytochem. 2014;62(10):698–738. PubMedPubMedCentralCrossRef

Galli SJ, Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Eur J Immunol. 2010;40(7):1843–51. PubMedPubMedCentralCrossRef

Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693–704. PubMedPubMedCentralCrossRef

Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8(3):183–92. PubMedCrossRef

Smarr CB, Bryce PJ, Miller SD. Antigen-specific tolerance in immunotherapy of Th2-associated allergic diseases. Crit Rev Immunol. 2013;33(5):389–414. PubMedPubMedCentralCrossRef

Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev. 1997;77(4):1033–79. PubMedCrossRef

Galli SJ, Gordon JR, Wershil BK. Cytokine production by mast cells and basophils. Curr Opin Immunol. 1991;3(6):865–72. PubMedCrossRef

10.

Galli SJ, Gordon JR, Wershil BK. Mast cell cytokines in allergy and inflammation. Agents Actions Suppl. 1993;43:209–20. PubMed

11.

Echtenacher B, Männel DN, Hültner L. Critical protective role of mast cells in a model of acute septic peritonitis. Nature. 1996;381(6577):75–7. PubMedCrossRef

12.

Galli SJ, Maurer M, Lantz CS. Mast cells as sentinels of innate immunity. Curr Opin Immunol. 1999;11(1):53–9. PubMedCrossRef

13.

Brown JM, Wilson TM, Metcalfe DD. The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clin Exp Allergy. 2008;38(1):4–18. PubMedCrossRef

14.

Fajt ML, Gelhaus SL, Freeman B, Uvalle CE, Trudeau JB, Holguin F, et al. Prostaglandin D ₂ pathway upregulation: relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol. 2013;131(6):1504–12. PubMedPubMedCentralCrossRef

15.

Kawakami T, Ando T, Kimura M, Wilson BS, Kawakami Y. Mast cells in atopic dermatitis. Curr Opin Immunol. 2009;21(6):666–78. PubMedPubMedCentralCrossRef

16.

Schuerwegh AJ, De Clerck LS, De Schutter L, Bridts CH, Verbruggen A, Stevens WJ. Flow cytometric detection of type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5) cytokines in T-helper and T-suppressor/cytotoxic cells in rheumatoid arthritis, allergic asthma and atopic dermatitis. Cytokine. 1999;11(10):783–8. PubMedCrossRef

17.

Johansson SGO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: report of the nomenclature review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832–6. PubMedCrossRef

18.

Voisin T, Bouvier A, Chiu IM. Neuro-immune interactions in allergic diseases: novel targets for therapeutics. Int Immunol. 2017;29(6):247–61. PubMedPubMedCentralCrossRef

19.

Kabata H, Artis D. Neuro-immune crosstalk and allergic inflammation. J Clin Invest. 2019;129(4):1475–82. PubMedPubMedCentralCrossRef

20.

Dothel G, Barbaro MR, Boudin H, Vasina V, Cremon C, Gargano L, et al. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2015;148(5):1002–1011.e4. PubMedCrossRef

21.

Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J. Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gastroenterology. 1989;97(3):575–85. PubMedCrossRef

22.

•• Green DP, Limjunyawong N, Gour N, Pundir P, Dong X. A mast cell-specific receptor mediates neurogenic inflammation and Pain. Neuron. 2019;101(3):412–420.e3 This study demonstrated novel role of MrgprB2 in neurogenic inflammation and pain. PubMedPubMedCentralCrossRef

23.

•• Meixiong J, Anderson M, Limjunyawong N, Sabbagh MF, Hu E, Mack MR, et al. Activation of mast-cell-expressed Mas-related G-protein-coupled receptors drives non-histaminergic itch. Immunity. 2019;50(5):1163–1171.e5 This study showed that MrgprB2 mediates non-histaminergic itch. PubMedPubMedCentralCrossRef

24.

Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM. Molecular signatures of G-protein-coupled receptors. Nature. 2013;494(7436):185–94. PubMedCrossRef

25.

Gurevich VV, Gurevich EV. GPCR signaling regulation: the role of GRKs and Arrestins. Front Pharmacol. 2019;10:125. PubMedPubMedCentralCrossRef

26.

Pitcher JA, Freedman NJ, Lefkowitz RJ. G protein-coupled receptor kinases. Annu Rev Biochem. 1998;67:653–92. PubMedCrossRef

27.

Subramanian H, Gupta K, Guo Q, Price R, Ali H. Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells. J Biol Chem. 2011;286(52):44739–49. PubMedPubMedCentralCrossRef

28.

Subramanian H, Gupta K, Lee D, Bayir AK, Ahn H, Ali H. β-Defensins activate human mast cells via Mas-related gene-X2 (MrgX2). J Immunol. 2013;191(1):345–52. PubMedPubMedCentralCrossRef

29.

McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519(7542):237–41. PubMedCrossRef

30.

Navinés-Ferrer A, Serrano-Candelas E, Lafuente A, Muñoz-Cano R, Martín M, Gastaminza G. MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia. Sci Rep. 2018;8(1):11628. PubMedPubMedCentralCrossRef

31.

Douglas SD, Leeman SE. Neurokinin-1 receptor: functional significance in the immune system in reference to selected infections and inflammation. Ann N Y Acad Sci. 2011;1217:83–95. PubMedCrossRef

32.

Bellucci F, Carini F, Catalani C, Cucchi P, Lecci A, Meini S, et al. Pharmacological profile of the novel mammalian tachykinin, hemokinin 1. Br J Pharmacol. 2002;135(1):266–74. PubMedPubMedCentralCrossRef

33.

Berger A, Paige CJ. Hemokinin-1 has substance P-like function in U-251 MG astrocytoma cells: a pharmacological and functional study. J Neuroimmunol. 2005;164(1–2):48–56. PubMedCrossRef

34.

•• Manorak W, Idahosa C, Gupta K, Roy S, Panettieri R, Ali H. Upregulation of Mas-related G protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1. Respir Res. 2018;19(1):1 This study showed that MRGPRX2 is upregulated in asthmatic lungs and that HK-1 activates MRGPRX2 not NK-1R. PubMedPubMedCentralCrossRef

35.

Varricchi G, Pecoraro A, Loffredo S, Poto R, Rivellese F, Genovese A, et al. Heterogeneity of human mast cells with respect to MRGPRX2 receptor expression and function. Front Cell Neurosci. 2019;13:299. PubMedPubMedCentralCrossRef

36.

Welle M. Development, significance, and heterogeneity of mast cells with particular regard to the mast cell-specific proteases chymase and tryptase. J Leukoc Biol. 1997;61(3):233–45. PubMedCrossRef

37.

Gurish MF, Austen KF. Developmental origin and functional specialization of mast cell subsets. Immunity. 2012;37(1):25–33. PubMedCrossRef

38.

Kulka M, Sheen CH, Tancowny BP, Grammer LC, Schleimer RP. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology. 2008;123(3):398–410. PubMedPubMedCentralCrossRef

39.

Bischoff SC, Schwengberg S, Lorentz A, Manns MP, Bektas H, Sann H, et al. Substance P and other neuropeptides do not induce mediator release in isolated human intestinal mast cells. Neurogastroenterol Motil. 2004;16(2):185–93. PubMedCrossRefPubMedCentral

40.

Sumpter TL, Ho CH, Pleet AR, Tkacheva OA, Shufesky WJ, Rojas-Canales DM, et al. Autocrine hemokinin-1 functions as endogenous adjuvant for IgE-mediated mast cell inflammatory responses. J Allergy Clin Immunol. 2015;135(4):1019–1030.e8. PubMedCrossRef

41.

Fujisawa D, Kashiwakura J-I, Kita H, Kikukawa Y, Fujitani Y, Sasaki-Sakamoto T, et al. Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J Allergy Clin Immunol. 2014;134(3):622–633.e9. PubMedCrossRef

42.

Tatemoto K, Nozaki Y, Tsuda R, Konno S, Tomura K, Furuno M, et al. Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun. 2006;349(4):1322–8. PubMedCrossRef

43.

Burstein ES, Ott TR, Feddock M, Ma J-N, Fuhs S, Wong S, et al. Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors. Br J Pharmacol. 2006;147(1):73–82. PubMedCrossRef

44.

Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138(3):700–10. PubMedPubMedCentralCrossRef

45.

•• Serhan N, Basso L, Sibilano R, Petitfils C, Meixiong J, Bonnart C, et al. House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation. Nat Immunol. 2019;20(11):1435–43 This important study implicated the novel role MrgprB2 as a facilitator of mast cell-nerve interaction in atopic dermatitis-like type 2 skin inflammation. PubMedPubMedCentralCrossRef

46.

•• An J, Lee J-H, Won H-K, Kang Y, Song W-J, Kwon H-S, et al. Clinical significance of serum MRGPRX2 as a new biomarker in allergic asthma. Allergy. 2020;75(4):959–62 This study identified upregulation of serum MRGPRX2 as a new biomarker for allergic asthma. PubMedCrossRef

47.

Taylor-Clark TE, Nassenstein C, Undem BJ. Leukotriene D4 increases the excitability of capsaicin-sensitive nasal sensory nerves to electrical and chemical stimuli. Br J Pharmacol. 2008;154(6):1359–68. PubMedPubMedCentralCrossRef

48.

Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000;6(2):151–8. PubMedCrossRef

49.

Shim W-S, Oh U. Histamine-induced itch and its relationship with pain. Mol Pain. 2008;4:29. PubMedPubMedCentralCrossRef

50.

• Forsythe P. Mast cells in neuroimmune interactions. Trends Neurosci. 2019;42(1):43–55 Excellent review on the role of mast cells in neuroimmune interaction. PubMedCrossRef

51.

Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018;40(3):249–59. PubMedPubMedCentralCrossRef

52.

Mashaghi A, Marmalidou A, Tehrani M, Grace PM, Pothoulakis C, Dana R. Neuropeptide substance P and the immune response. Cell Mol Life Sci. 2016;73(22):4249–64. PubMedPubMedCentralCrossRef

53.

O’Connor TM, O’Connell J, O’Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol. 2004;201(2):167–80. PubMedCrossRef

54.

Chu HW, Kraft M, Krause JE, Rex MD, Martin RJ. Substance P and its receptor neurokinin 1 expression in asthmatic airways. J Allergy Clin Immunol. 2000;106(4):713–22. PubMedCrossRef

55.

Morteau O, Lu B, Gerard C, Gerard NP. Hemokinin 1 is a full agonist at the substance P receptor. Nat Immunol. 2001;2(12):1088. PubMedCrossRef

56.

Maggi CA. The effects of tachykinins on inflammatory and immune cells. Regul Pept. 1997;70(2–3):75–90. PubMedCrossRef

57.

Steinhoff MS, von Mentzer B, Geppetti P, Pothoulakis C, Bunnett NW. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev. 2014;94(1):265–301. PubMedPubMedCentralCrossRef

58.

Garcia-Recio S, Gascón P. Biological and pharmacological aspects of the NK1-receptor. Biomed Res Int. 2015;2015:495704. PubMedPubMedCentralCrossRef

59.

Pintér E, Pozsgai G, Hajna Z, Helyes Z, Szolcsányi J. Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions. Br J Clin Pharmacol. 2014;77(1):5–20. PubMedCrossRef

60.

Ramalho R, Soares R, Couto N, Moreira A. Tachykinin receptors antagonism for asthma: a systematic review. BMC Pulm Med. 2011;11:41. PubMedPubMedCentralCrossRef

61.

Boot JD, de Haas S, Tarasevych S, Roy C, Wang L, Amin D, et al. Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med. 2007;175(5):450–7. PubMedCrossRef

62.

Borsook D, Upadhyay J, Klimas M, Schwarz AJ, Coimbra A, Baumgartner R, et al. Decision-making using fMRI in clinical drug development: revisiting NK-1 receptor antagonists for pain. Drug Discov Today. 2012;17(17–18):964–73. PubMedCrossRef

63.

Lönndahl L, Holst M, Bradley M, Killasli H, Heilborn J, Hall MA, et al. Substance P antagonist aprepitant shows no additive effect compared with standardized topical treatment alone in patients with atopic dermatitis. Acta Derm Venereol. 2018;98(3):324–8. PubMedCrossRef

64.

Azimi E, Reddy VB, Shade K-TC, Anthony RM, Talbot S, Pereira PJS, et al. Dual action of neurokinin-1 antagonists on Mas-related GPCRs. JCI Insight. 2016;1(16):e89362. PubMedPubMedCentralCrossRef

65.

Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109–22. PubMedCrossRef

66.

Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66(Suppl. 1):8–16. PubMedCrossRef

67.

Saunders SP, Moran T, Floudas A, Wurlod F, Kaszlikowska A, Salimi M, et al. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity. J Allergy Clin Immunol. 2016;137(2):482–91. PubMedPubMedCentralCrossRef

68.

Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283–9. PubMedCrossRef

69.

Ring J, Zink A, Arents BWM, Seitz IA, Mensing U, Schielein MC, et al. Atopic eczema: burden of disease and individual suffering - results from a large EU study in adults. J Eur Acad Dermatol Venereol. 2019;33(7):1331–40. PubMedCrossRef

70.

Silverberg JI. Comorbidities and the impact of atopic dermatitis. Ann Allergy Asthma Immunol. 2019;123(2):144–51. CrossRefPubMed

71.

Ahn K, Kim BE, Kim J, Leung DY. Recent advances in atopic dermatitis. Curr Opin Immunol. 2020;66:14–21. PubMedCrossRef

72.

Werfel T, Allam J-P, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(2):336–49. PubMedCrossRef

73.

Ong PY. New insights in the pathogenesis of atopic dermatitis. Pediatr Res. 2014;75(1–2):171–5. PubMedCrossRef

74.

Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship. Trends Microbiol. 2018;26(6):484–97. PubMedCrossRef

75.

Park H-Y, Kim C-R, Huh I-S, Jung M-Y, Seo E-Y, Park J-H, et al. Staphylococcus aureus colonization in acute and chronic skin lesions of patients with atopic dermatitis. Ann Dermatol. 2013;25(4):410–6. PubMedPubMedCentralCrossRef

76.

Totté JEE, van der Feltz WT, Hennekam M, van Belkum A, van Zuuren EJ, Pasmans SGMA. Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol. 2016;175(4):687–95. PubMedCrossRef

77.

Bunikowski R, Mielke ME, Skarabis H, Worm M, Anagnostopoulos I, Kolde G, et al. Evidence for a disease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol. 2000;105(4):814–9. PubMedCrossRef

78.

Liu F-T, Goodarzi H, Chen H-Y. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011;41(3):298–310. PubMedCrossRef

79.

Forsythe P, Bienenstock J. The mast cell-nerve functional unit: a key component of physiologic and pathophysiologic responses. Chem Immunol Allergy. 2012;98:196–221. PubMedCrossRef

80.

Järvikallio A, Harvima IT, Naukkarinen A. Mast cells, nerves and neuropeptides in atopic dermatitis and nummular eczema. Arch Dermatol Res. 2003;295(1):2–7. PubMedCrossRef

81.

Salomon J, Baran E. The role of selected neuropeptides in pathogenesis of atopic dermatitis. J Eur Acad Dermatol Venereol. 2008;22(2):223–8. PubMed

82.

Toyoda M, Nakamura M, Makino T, Fuh H, Kagoura M, Morohashi M. Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol. 2002;147(1):71–9. PubMedCrossRef

83.

Usoskin D, Furlan A, Islam S, Abdo H, Lönnerberg P, Lou D, et al. Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat Neurosci. 2015;18(1):145–53. PubMedCrossRef

84.

Kawakami Y, Yumoto K, Kawakami T. An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases. Allergol Int. 2007;56(4):403–9. PubMedCrossRef

85.

Kawakami Y, Kawakami T. A mouse model of atopic dermatitis. Methods Mol Biol. 2015;1220:497–502. PubMedCrossRef

86.

Yang T-LB, Kim BS. Pruritus in allergy and immunology. J Allergy Clin Immunol. 2019;144(2):353–60. PubMedPubMedCentralCrossRef

87.

• Gupta K, Harvima IT. Mast cell-neural interactions contribute to pain and itch. Immunol Rev. 2018;282(1):168–87 Informative review on the role of mast cell-nerve interaction in pain and itch. PubMedPubMedCentralCrossRef

88.

Siiskonen H, Harvima I. Mast cells and sensory nerves contribute to neurogenic inflammation and pruritus in chronic skin inflammation. Front Cell Neurosci. 2019;13:422. PubMedPubMedCentralCrossRef

89.

Yosipovitch G, Berger T, Fassett MS. Neuroimmune interactions in chronic itch of atopic dermatitis. J Eur Acad Dermatol Venereol. 2020;34(2):239–50. PubMedCrossRef

90.

Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16(11):1267–76. PubMedPubMedCentralCrossRef

91.

Uehara M, Sawai T. A longitudinal study of contact sensitivity in patients with atopic dermatitis. Arch Dermatol. 1989;125(3):366–8. PubMedCrossRef

92.

Zheng Y, Che D, Peng B, Hao Y, Zhang X, He L, et al. All-trans-retinoic acid activated mast cells via Mas-related G-protein-coupled receptor-X2 in retinoid dermatitis. Contact Dermatitis. 2019;81(3):184–93. PubMedCrossRef

93.

Peng B, Che D, Hao Y, Zheng Y, Liu R, Qian Y, et al. Thimerosal induces skin pseudo-allergic reaction via Mas-related G-protein coupled receptor B2. J Dermatol Sci. 2019;95(3):99–106. PubMedCrossRef

94.

Brightling CE, Bradding P. The re-emergence of the mast cell as a pivotal cell in asthma pathogenesis. Curr Allergy Asthma Rep. 2005;5(2):130–5. PubMedCrossRef

95.

Page S, Ammit AJ, Black JL, Armour CL. Human mast cell and airway smooth muscle cell interactions: implications for asthma. Am J Phys Lung Cell Mol Phys. 2001;281(6):L1313–23.

96.

Robinson DS. The role of the mast cell in asthma: induction of airway hyperresponsiveness by interaction with smooth muscle? J Allergy Clin Immunol. 2004;114(1):58–65. PubMedCrossRef

97.

Andersson CK, Bergqvist A, Mori M, Mauad T, Bjermer L, Erjefält JS. Mast cell-associated alveolar inflammation in patients with atopic uncontrolled asthma. J Allergy Clin Immunol. 2011;127(4):905–912.e1–7. PubMedCrossRef

98.

Andersson C, Tufvesson E, Diamant Z, Bjermer L. Revisiting the role of the mast cell in asthma. Curr Opin Pulm Med. 2016;22(1):10–7. PubMedCrossRef

99.

Kubo M. Innate and adaptive type 2 immunity in lung allergic inflammation. Immunol Rev. 2017;278(1):162–72. PubMedCrossRef

100.

Hallstrand TS, Henderson WR. An update on the role of leukotrienes in asthma. Curr Opin Allergy Clin Immunol. 2010;10(1):60–6. PubMedPubMedCentralCrossRef

101.

• Méndez-Enríquez E, Hallgren J. Mast cells and their progenitors in allergic asthma. Front Immunol. 2019;10:821 Excellent overview of the role of mast cells in allergic asthma. PubMedPubMedCentralCrossRef

102.

Undem BJ, Riccio MM, Weinreich D, Ellis JL, Myers AC. Neurophysiology of mast cell-nerve interactions in the airways. Int Arch Allergy Immunol. 1995;107(1–3):199–201. PubMedCrossRef

103.

Caubet J-C, Eigenmann PA. Allergic triggers in atopic dermatitis. Immunol Allergy Clin N Am. 2010;30(3):289–307. CrossRef

104.

Singh M, Hays A. Indoor and outdoor allergies. Prim Care. 2016;43(3):451–63. PubMedCrossRef

105.

Tomaki M, Ichinose M, Miura M, Hirayama Y, Yamauchi H, Nakajima N, et al. Elevated substance P content in induced sputum from patients with asthma and patients with chronic bronchitis. Am J Respir Crit Care Med. 1995;151(3 Pt 1):613–7. PubMedCrossRef

106.

Nieber K, Baumgarten CR, Rathsack R, Furkert J, Oehme P, Kunkel G. Substance P and β-endorphin-like immunoreactivity in lavage fluids of subjects with and without allergic asthma. J Allergy Clin Immunol. 1992;90(4, Part 1):646–52. PubMedCrossRef

107.

Heaney LG, Cross LJ, Stanford CF, Ennis M. Substance P induces histamine release from human pulmonary mast cells. Clin Exp Allergy. 1995;25(2):179–86. PubMedCrossRef

108.

Kajiwara N, Sasaki T, Bradding P, Cruse G, Sagara H, Ohmori K, et al. Activation of human mast cells through the platelet-activating factor receptor. J Allergy Clin Immunol. 2010;125(5):1137–1145.e6. PubMedCrossRef

109.

•• Plum T, Wang X, Rettel M, Krijgsveld J, Feyerabend TB, Rodewald H-R. Human mast cell proteome reveals unique lineage, putative functions, and structural basis for cell ablation. Immunity. 2020;52(2):404–416.e5 Important study that showed MRGPRX2 is expressed in lung mast cells as opposed to previous observation that it was not. PubMedCrossRef

110.

Balzar S, Fajt ML, Comhair SAA, Erzurum SC, Bleecker E, Busse WW, et al. Mast cell phenotype, location, and activation in severe asthma. Data from the severe asthma research program. Am J Respir Crit Care Med. 2011;183(3):299–309. PubMedCrossRef

111.

Sverrild A, Bergqvist A, Baines KJ, Porsbjerg C, Andersson CK, Thomsen SF, et al. Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation. Clin Exp Allergy. 2016;46(2):288–97. PubMedCrossRef

112.

Zhang Y, Lu L, Furlonger C, Wu GE, Paige CJ. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat Immunol. 2000;1(5):392–7. PubMedCrossRef

113.

Grassin-Delyle S, Naline E, Buenestado A, Risse P-A, Sage E, Advenier C, et al. Expression and function of human hemokinin-1 in human and Guinea pig airways. Respir Res. 2010;11:139. PubMedPubMedCentralCrossRef

114.

Amin K, Janson C, Bystrom J. Role of eosinophil granulocytes in allergic airway inflammation endotypes. Scand J Immunol. 2016;84(2):75–85. PubMedCrossRef

115.

Doran E, Cai F, Holweg CTJ, Wong K, Brumm J, Arron JR. Interleukin-13 in asthma and other eosinophilic disorders. Front Med (Lausanne). 2017;4:139. CrossRef

116.

Yasukawa A, Hosoki K, Toda M, Miyake Y, Matsushima Y, Matsumoto T, et al. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells. PLoS One. 2013;8(5):e64281. PubMedPubMedCentralCrossRef

117.

Duits LA, Nibbering PH, van Strijen E, Vos JB, Mannesse-Lazeroms SPG, van Sterkenburg MAJA, et al. Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol Med Microbiol. 2003;38(1):59–64.

118.

Proud D, Sanders SP, Wiehler S. Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. J Immunol. 2004;172(7):4637–45.

119.

•• Alkanfari I, Gupta K, Jahan T, Ali H. Naturally occurring missense MRGPRX2 variants display loss of function phenotype for mast cell degranulation in response to substance P, hemokinin-1, human β-defensin-3, and icatibant. J Immunol. 2018;201(2):343–9 This study identified naturally occurring MRGPRX2 variants with a loss of function phenotype in response to SP and HK-1 induced mast cell degranulation. PubMedPubMedCentralCrossRef

120.

Lansu K, Karpiak J, Liu J, Huang X-P, McCorvy JD, Kroeze WK, et al. In silico design of novel probes for the atypical opioid receptor MRGPRX2. Nat Chem Biol. 2017;13(5):529–36. PubMedPubMedCentralCrossRef

121.

Reddy VB, Graham TA, Azimi E, Lerner EA. A single amino acid in MRGPRX2 necessary for binding and activation by pruritogens. J Allergy Clin Immunol. 2017;140(6):1726–8. PubMedPubMedCentralCrossRef

122.

Venkatakrishnan AJ, Deupi X, Lebon G, Heydenreich FM, Flock T, Miljus T, et al. Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region. Nature. 2016;536(7617):484–7. PubMedPubMedCentralCrossRef

123.

•• Chompunud Na Ayudhya C, Roy S, Alkanfari I, Ganguly A, Ali H. Identification of gain and loss of function missense variants in MRGPRX2’s transmembrane and intracellular domains for mast cell activation by substance P. Int J Mol Sci. 2019;20(21):5247. This study identified both gain and loss of function variants of MRGPRX2 for SP induced mast cell activation with prospective direct clinical relevance.

124.

Ali H. Mas-related G protein coupled receptor-X2: a potential new target for modulating mast cell-mediated allergic and inflammatory diseases. J Immunobiol. 2016;1(4):115.

125.

Ogasawara H, Furuno M, Edamura K, Noguchi M. Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells. J Leukoc Biol. 2019;106(5):1069–77. PubMedCrossRef

126.

Burton OT, Stranks AJ, Tamayo JM, Koleoglou KJ, Schwartz LB, Oettgen HC. A humanized mouse model of anaphylactic peanut allergy. J Allergy Clin Immunol. 2017;139(1):314–322.e9. PubMedCrossRef

127.

Bryce PJ, Falahati R, Kenney LL, Leung J, Bebbington C, Tomasevic N, et al. Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis. J Allergy Clin Immunol. 2016;138(3):769–79. PubMedPubMedCentralCrossRef

128.

Ito R, Maruoka S, Gon Y, Katano I, Takahashi T, Ito M, et al. Recent advances in allergy research using humanized mice. Int J Mol Sci. 2019;20(11):2740. PubMedCentralCrossRefPubMed

129.

• Mencarelli A, Gunawan M, Yong KSM, Bist P, Tan WWS, Tan SY, et al. A humanized mouse model to study mast cells mediated cutaneous adverse drug reactions. J Leukoc Biol. 2020;107(5):797–807 This study established a humanized mice model expressing MRGPRX2 to address species-specific limitation in in vivo studies. PubMedPubMedCentralCrossRef

Titel: Mast Cell-Specific MRGPRX2: a Key Modulator of Neuro-Immune Interaction in Allergic Diseases
Autoren:: Monica Thapaliya
Chalatip Chompunud Na Ayudhya
Aetas Amponnawarat
Saptarshi Roy
Hydar Ali
Publikationsdatum: 01.01.2021
DOI: https://doi.org/10.1007/s11882-020-00979-5
Verlag: Springer US
Zeitschrift: Current Allergy and Asthma Reports
Ausgabe 1/2021
Print ISSN: 1529-7322
Elektronische ISSN: 1534-6315

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Mast Cell-Specific MRGPRX2: a Key Modulator of Neuro-Immune Interaction in Allergic Diseases

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Springer Medizin

Publisher’s Note

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Purpose of Review

Recent Findings

Summary

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