Charcot-Leyden Crystals in Eosinophilic Inflammation: Active Cytolysis Leads to Crystal Formation

  • Shigeharu UekiEmail author
  • Yui Miyabe
  • Yohei Yamamoto
  • Mineyo Fukuchi
  • Makoto Hirokawa
  • Lisa A. Spencer
  • Peter F. Weller
Otitis (DP Skoner, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Otitis


Purpose of Review

Charcot-Leyden crystals (CLCs), slender bipyramidal hexagonal crystals, were first described by Jean-Martin Charcot in 1853, predating Paul Ehrlich’s “discovery” of eosinophils by 26 years. To date, CLCs are known as a classical hallmark of eosinophilic inflammation. CLC protein expresses palmitate cleaving lysophospholipase activity and is a member of the family of S-type lectins, galectin-10. We summarize current knowledge regarding the pathological observations of CLCs and their mechanism of generation focusing on eosinophil cell death.

Recent Findings

The presence of CLCs in vivo has been consistently associated with lytic eosinophils. Recent evidence revealed that cytolysis represents the occurrence of extracellular trap cell death (ETosis), an active non-apoptotic cell death process releasing filamentous chromatin structure. Galectin-10 is a predominant protein present within the cytoplasm of eosinophils but not stored in secretory granules. Activated eosinophils undergo ETosis and loss of galectin-10 cytoplasmic localization results in intracellular CLC formation. Free galectin-10 released following plasma membrane disintegration forms extracellular CLCs. Of interest, galectin-10-containing extracellular vesicles are also released during ETosis. Mice models indicated that CLCs could be a novel therapeutic target for Th2-type airway inflammation.


The concept of ETosis, which represents a major fate of activated eosinophils, expands our current understanding by which cytoplasmic galectin-10 is crystalized/externalized. Besides CLCs and free galectin-10, cell-free granules, extracellular chromatin traps, extracellular vesicles, and other alarmins, all released through the process of ETosis, have novel implications in various eosinophilic disorders.


Charcot-Leyden crystal Degranulation Extracellular traps Eosinophils Galectin-10 



Charcot-Leyden crystal


Chronic rhinosinusitis with nasal polyps


Eosinophil extracellular trap cell death


Extracellular trap cell death


Extracellular traps, DNA traps


Extracellular vesicle


Neutrophil extracellular trap cell death



The authors are grateful to Satomi Misawa for outstanding assistance in drawing the figure.

Funding Information

This study was funded in part by a Research Grant on Allergic Disease and Immunology from the Japan Agency for Medical Research and Development (JP19ek0410055), Charitable Trust Laboratory Medicine Research Foundation of Japan, Japanese Society of Laboratory Medicine Fund for Promotion of Scientific Research, and JSPS KAKENHI 15KK0329, 16K08926 (SU), NIH R37AI020241 (PFW), and NIH R01AI121186 (LAS).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Sakula A. Charcot-Leyden crystals and Curschmann spirals in asthmatic sputum. Thorax. 1986;41(7):503–7.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Samter M. Charcot-Leyden crystals. J Allergy. 1947;18(4):221–30.PubMedGoogle Scholar
  3. 3.
    Su J. A brief history of Charcot-Leyden crystal protein/galectin-10 research. Molecules. 2018;23(11).PubMedCentralGoogle Scholar
  4. 4.
    Ayres WW, Starkey NM. Studies on Charcot-Leyden crystals. Blood. 1950;5(3):254–66.PubMedGoogle Scholar
  5. 5.
    Dawe CJ, Williams WL. Histochemical studies of Charcot-Leyden crystals. Anat Rec. 1953;116(1):53–74.PubMedGoogle Scholar
  6. 6.
    Ackerman SJ, Loegering DA, Gleich GJ. The human eosinophil Charcot-Leyden crystal protein: biochemical characteristics and measurement by radioimmunoassay. J Immunol. 1980;125(5):2118–26.PubMedGoogle Scholar
  7. 7.
    Ackerman SJ, Corrette SE, Rosenberg HF, Bennett JC, Mastrianni DM, Nicholson-Weller A, et al. Molecular cloning and characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase). Similarities to IgE binding proteins and the S-type animal lectin superfamily. J Immunol. 1993;150(2):456–68.PubMedGoogle Scholar
  8. 8.
    Weller PF, Bach D, Austen KF. Human eosinophil lysophospholipase: the sole protein component of Charcot-Leyden crystals. J Immunol. 1982;128(3):1346–9.PubMedGoogle Scholar
  9. 9.
    Weller PF, Goetzl EJ, Austen KF. Identification of human eosinophil lysophospholipase as the constituent of Charcot-Leyden crystals. Proc Natl Acad Sci U S A. 1980;77(12):7440–3.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Weller PF, Bach DS, Austen KF. Biochemical characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase). J Biol Chem. 1984;259(24):15100–5.PubMedGoogle Scholar
  11. 11.
    Leonidas DD, Elbert BL, Zhou Z, Leffler H, Ackerman SJ, Acharya KR. Crystal structure of human Charcot–Leyden crystal protein, an eosinophil lysophospholipase, identifies it as a new member of the carbohydrate-binding family of galectins. Structure. 1995;3(12):1379–93.PubMedGoogle Scholar
  12. 12.
    Acharya KR, Ackerman SJ. Eosinophil granule proteins: form and function. J Biol Chem. 2014;289(25):17406–15.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Choi E, Miller AD, Devenish E, Asakawa M, McConkey M, Peters-Kennedy J. Charcot-Leyden crystals: do they exist in veterinary species? A case report and literature review. J Vet Diagn Investig. 2017;29(6):904–9.Google Scholar
  14. 14.
    Guo L, Johnson RS, Schuh JC. Biochemical characterization of endogenously formed eosinophilic crystals in the lungs of mice. J Biol Chem. 2000;275(11):8032–7.PubMedGoogle Scholar
  15. 15.
    Dunphy JL, Barcham GJ, Bischof RJ, Young AR, Nash A, Meeusen EN. Isolation and characterization of a novel eosinophil-specific galectin released into the lungs in response to allergen challenge. J Biol Chem. 2002;277(17):14916–24.PubMedGoogle Scholar
  16. 16.
    Young AR, Barcham GJ, Kemp JM, Dunphy JL, Nash A, Meeusen EN. Functional characterization of an eosinophil-specific galectin, ovine galectin-14. Glycoconj J. 2009;26(4):423–32.PubMedGoogle Scholar
  17. 17.
    Wilkerson EM, Johansson MW, Hebert AS, Westphall MS, Mathur SK, Jarjour NN, et al. The peripheral blood eosinophil proteome. J Proteome Res. 2016;15(5):1524–33.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kubach J, Lutter P, Bopp T, Stoll S, Becker C, Huter E, et al. Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood. 2007;110(5):1550–8.PubMedGoogle Scholar
  19. 19.
    Noh S, Jin S, Park CO, Lee YS, Lee N, Lee J, et al. Elevated galectin-10 expression of IL-22-producing T cells in patients with atopic dermatitis. J Investig Dermatol. 2016;136(1):328–31.PubMedGoogle Scholar
  20. 20.
    Ali ND, Weissmann D. Charcot-Leyden crystals in T-cell lymphoblastic lymphoma. Blood. 2017;129(3):394.PubMedGoogle Scholar
  21. 21.
    Staribratova D, Belovejdov V, Staikov D, Dikov D. Demonstration of Charcot-Leyden crystals in eosinophilic cystitis. Archives of pathology & laboratory medicine. 2010;134(10):1420.Google Scholar
  22. 22.
    Manny JS, Ellis LR. Acute myeloid leukemia with Charcot-Leyden crystals. Blood. 2012;120(3):503.PubMedGoogle Scholar
  23. 23.
    Ikeda H, Katayanagi K, Kurumaya H, Harada K, Sato Y, Sasaki M, et al. A case of hypereosinophilia-associated multiple mass lesions of liver showing non-granulomatous eosinophilic hepatic necrosis. Gastroenterol Res. 2011;4(4):168–73.Google Scholar
  24. 24.
    Thakral D, Agarwal P, Saran RK, Saluja S. Significance of Charcot Leyden crystals in liver cytology-a case report. Diagn Cytopathol. 2015;43(5):392–4.PubMedGoogle Scholar
  25. 25.
    Muller W, Firsching R. Significance of eosinophilic granulocytes in chronic subdural hematomas. Neurosurg Rev. 1990;13(4):305–8.PubMedGoogle Scholar
  26. 26.
    •• Ueki S, Tokunaga T, Melo RCN, Saito H, Honda K, Fukuchi M, et al. Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death. Blood. 2018;132(20):2183–7 This research reveals an active process by which Charcot-Leyden crystals are formed in eosinophilic diseases.PubMedGoogle Scholar
  27. 27.
    Melo RCN, Weller PF. Contemporary understanding of the secretory granules in human eosinophils. J Leukoc Biol. 2018;104(1):85–93.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17(12):746–60.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Spencer LA, Bonjour K, Melo RC, Weller PF. Eosinophil secretion of granule-derived cytokines. Front Immunol. 2014;5:496.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Dvorak AM, Letourneau L, Login GR, Weller PF, Ackerman SJ. Ultrastructural localization of the Charcot-Leyden crystal protein (lysophospholipase) to a distinct crystalloid-free granule population in mature human eosinophils. Blood. 1988;72(1):150–8.PubMedGoogle Scholar
  31. 31.
    Calafat J, Janssen H, Knol EF, Weller PF, Egesten A. Ultrastructural localization of Charcot-Leyden crystal protein in human eosinophils and basophils. Eur J Haematol. 1997;58(1):56–66.PubMedGoogle Scholar
  32. 32.
    Erjefalt JS, Persson CG. New aspects of degranulation and fates of airway mucosal eosinophils. Am J Respir Crit Care Med. 2000;161(6):2074–85.PubMedGoogle Scholar
  33. 33.
    Watanabe K, Misu T, Inoue S, Edamatsu H. Cytolysis of eosinophils in nasal secretions. Ann Otol Rhinol Laryngol. 2003;112(2):169–73.PubMedGoogle Scholar
  34. 34.
    Uller L, Andersson M, Greiff L, Persson CG, Erjefalt JS. Occurrence of apoptosis, secondary necrosis, and cytolysis in eosinophilic nasal polyps. Am J Respir Crit Care Med. 2004;170(7):742–7.PubMedGoogle Scholar
  35. 35.
    Persson C, Ueki S. Lytic eosinophils produce extracellular DNA traps as well as free eosinophil granules. J Allergy Clin Immunol. 2018;141(3):1164.PubMedGoogle Scholar
  36. 36.
    Persson CG, Erjefalt JS. Eosinophil lysis and free granules: an in vivo paradigm for cell activation and drug development. Trends Pharmacol Sci. 1997;18(4):117–23.PubMedGoogle Scholar
  37. 37.
    Ueki S, Melo RC, Ghiran I, Spencer LA, Dvorak AM, Weller PF. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood. 2013;121(11):2074–83.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Ueki S, Tokunaga T, Fujieda S, Honda K, Hirokawa M, Spencer LA, et al. Eosinophil ETosis and DNA traps: a new look at eosinophilic inflammation. Curr Allergy Asthma Rep. 2016;16(8):54.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Choi Y, Lee Y, Park HS. Which factors associated with activated eosinophils contribute to the pathogenesis of aspirin-exacerbated respiratory disease? Allergy Asthma Immunol Res. 2019;11(3):320–9.PubMedGoogle Scholar
  40. 40.
    Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176(2):231–41.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Sorensen OE, Borregaard N. Neutrophil extracellular traps - the dark side of neutrophils. J Clin Invest. 2016;126(5):1612–20.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Brinkmann V. Neutrophil extracellular traps in the second decade. J Innate Immun. 2018;10(5–6):414–21.PubMedGoogle Scholar
  43. 43.
    Fukuchi M, Ueki S, Saito H, Miyabe Y, Konno Y, Omokawa A, et al. Comparison of CD16-negative selection vs. MACSxpress system for isolation of blood eosinophils. Allergol Int. 2019.Google Scholar
  44. 44.
    Yamauchi Y, Ueki S, Konno Y, Ito W, Takeda M, Nakamura Y, et al. The effect of hepatocyte growth factor on secretory functions in human eosinophils. Cytokine. 2016;88:45–50.PubMedGoogle Scholar
  45. 45.
    Ueki S, Konno Y, Takeda M, Moritoki Y, Hirokawa M, Matsuwaki Y, et al. Eosinophil extracellular trap cell death-derived DNA traps: their presence in secretions and functional attributes. J Allergy Clin Immunol. 2016;137(1):258–67.PubMedGoogle Scholar
  46. 46.
    Mukherjee M, Lacy P, Ueki S. Eosinophil extracellular traps and inflammatory pathologies-untangling the web! Front Immunol. 2018;9:2763.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Hellmark T, Ohlsson S, Pettersson A, Hansson M, Johansson ACM. Eosinophils in anti-neutrophil cytoplasmic antibody associated vasculitis. BMC Rheumatol. 2019;3:9.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Mukherjee M, Bulir DC, Radford K, Kjarsgaard M, Huang CM, Jacobsen EA, et al. Sputum autoantibodies in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2018;141(4):1269–79.PubMedGoogle Scholar
  49. 49.
    Choi Y, Le Pham D, Lee DH, Lee SH, Kim SH, Park HS. Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma. Exp Mol Med. 2018;50(8):104.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Muniz VS, Silva JC, Braga YAV, Melo RCN, Ueki S, Takeda M, et al. Eosinophils release extracellular DNA traps in response to Aspergillus fumigatus. J Allergy Clin Immunol. 2018;141(2):571–85 e7.PubMedGoogle Scholar
  51. 51.
    Omokawa A, Ueki S, Kikuchi Y, Takeda M, Asano M, Sato K, et al. Mucus plugging in allergic bronchopulmonary aspergillosis: implication of the eosinophil DNA traps. Allergol Int. 2018;67(2):280–2.PubMedGoogle Scholar
  52. 52.
    Ohta N, Ueki S, Konno Y, Hirokawa M, Kubota T, Tomioka-Matsutani S, et al. ETosis-derived DNA trap production in middle ear effusion is a common feature of eosinophilic otitis media. Allergol Int. 2018;67(3):414–6.PubMedGoogle Scholar
  53. 53.
    •• Persson EK, Verstraete K, Heyndrickx I, Gevaert E, Aegerter H, Percier J-M, et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science. 2019;364(6442) This study shows the first demonstration of CLC-dissolving antibody as a therapeutic modality for CLC-triggered Th2 airway inflammation.PubMedGoogle Scholar
  54. 54.
    Wouters J, Waelkens E, Vandoninck S, Segaert S, van den Oord JJ. Mass spectrometry of flame figures. Acta Derm Venereol. 2015;95(6):734–5.PubMedGoogle Scholar
  55. 55.
    Uribe Echevarria L, Leimgruber C, Garcia Gonzalez J, Nevado A, Alvarez R, Garcia LN, et al. Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease? Int J Chron Obstruct Pulmon Dis. 2017;12:885–96.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Muniz VS, Baptista-Dos-Reis R, Neves JS. Functional extracellular eosinophil granules: a bomb caught in a trap. Int Arch Allergy Immunol. 2013;162(4):276–82.PubMedGoogle Scholar
  57. 57.
    Ueki S, Ohta N, Takeda M, Konno Y, Hirokawa M. Eosinophilic otitis media: the aftermath of eosinophil extracellular trap cell death. Curr Allergy Asthma Rep. 2017;17(5):33.PubMedGoogle Scholar
  58. 58.
    Ueki S, Hebisawa A, Kitani M, Asano K, Neves JS. Allergic bronchopulmonary aspergillosis–a luminal hypereosinophilic disease with extracellular trap cell death. Front Immunol. 2018;9.Google Scholar
  59. 59.
    Papayannopoulos V, Staab D, Zychlinsky A. Neutrophil elastase enhances sputum solubilization in cystic fibrosis patients receiving DNase therapy. PLoS One. 2011;6(12):e28526.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.PubMedGoogle Scholar
  61. 61.
    Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, et al. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog. 2009;5(10):e1000639.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Munoz-Caro T, Rubio RM, Silva LM, Magdowski G, Gartner U, McNeilly TN, et al. Leucocyte-derived extracellular trap formation significantly contributes to Haemonchus contortus larval entrapment. Parasit Vectors. 2015;8:607.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Neubert E, Meyer D, Rocca F, Gunay G, Kwaczala-Tessmann A, Grandke J, et al. Chromatin swelling drives neutrophil extracellular trap release. Nat Commun. 2018;9(1):3767.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Klion AD. Charcot-Leyden crystals: solving an enigma. Blood. 2018;132(20):2111–2.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Mulay SR, Anders HJ. Crystallopathies. N Engl J Med. 2016;374(25):2465–76.PubMedGoogle Scholar
  66. 66.
    So AK, Martinon F. Inflammation in gout: mechanisms and therapeutic targets. Nat Rev Rheumatol. 2017;13(11):639–47.PubMedGoogle Scholar
  67. 67.
    Lao LM, Kumakiri M, Nakagawa K, Ishida H, Ishiguro K, Yanagihara M, et al. The ultrastructural findings of Charcot-Leyden crystals in stroma of mastocytoma. J Dermatol Sci. 1998;17(3):198–204.PubMedGoogle Scholar
  68. 68.
    Dvorak AM, Furitsu T, Letourneau L, Ishizaka T, Ackerman SJ. Mature eosinophils stimulated to develop in human cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. Part I. Piecemeal degranulation of specific granules and distribution of Charcot-Leyden crystal protein. Am J Pathol 1991;138(1):69–82.Google Scholar
  69. 69.
    Swanson EJ, Manivel JC, Valen PA, Mesa H. Necrotizing eosinophilic granulomatous lymphadenitis with ring- and C-shaped granulomas—an underrecognized specific manifestation of nodal Churg-Strauss syndrome. J Hematop. 2017;10(1):39–45.Google Scholar
  70. 70.
    •• Rodriguez-Alcazar JF, Ataide MA, Engels G, Schmitt-Mabmunyo C, Garbi N, Kastenmuller W, et al. Charcot-Leyden crystals activate the NLRP3 inflammasome and cause IL-1beta inflammation in human macrophages. J Immunol. 2019;202(2):550–8 This study shows the first demonstration of functional roles of CLCs.PubMedGoogle Scholar
  71. 71.
    Wahlund CJE, Eklund A, Grunewald J, Gabrielsson S. Pulmonary extracellular vesicles as mediators of local and systemic inflammation. Front Cell Dev Biol. 2017;5:39.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Akuthota P, Carmo LAS, Bonjour K, Murphy RO, Silva TP, Gamalier JP, et al. Extracellular microvesicle production by human eosinophils activated by “inflammatory” stimuli. Front Cell Dev Biol. 2016;4.Google Scholar
  73. 73.
    Negrete-Garcia MC, Jimenez-Torres CY, Alvarado-Vasquez N, Montes-Vizuet AR, Velazquez-Rodriguez JR, Jimenez-Martinez MC, et al. Galectin-10 is released in the nasal lavage fluid of patients with aspirin-sensitive respiratory disease. ScientificWorldJournal. 2012;2012:474020.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Ghafouri B, Irander K, Lindbom J, Tagesson C, Lindahl M. Comparative proteomics of nasal fluid in seasonal allergic rhinitis. J Proteome Res. 2006;5(2):330–8.PubMedGoogle Scholar
  75. 75.
    Chua JC, Douglass JA, Gillman A, O’Hehir RE, Meeusen EN. Galectin-10, a potential biomarker of eosinophilic airway inflammation. PLoS One. 2012;7(8):e42549.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Saffari H, Hoffman LH, Peterson KA, Fang JC, Leiferman KM, Pease LF 3rd, et al. Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2014;133(6):1728–34 e1.PubMedGoogle Scholar
  77. 77.
    Furuta GT, Kagalwalla AF, Lee JJ, Alumkal P, Maybruck BT, Fillon S, et al. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut. 2013;62(10):1395–405.PubMedGoogle Scholar
  78. 78.
    Wu D, Yan B, Wang Y, Zhang L, Wang C. Charcot-Leyden crystal concentration in nasal secretions predicts clinical response to glucocorticoids in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2019.Google Scholar
  79. 79.
    Pace KE, Hahn HP, Pang M, Nguyen JT, Baum LG. Cutting edge: CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death. J Immunol. 2000;165(5):2331–4.PubMedGoogle Scholar
  80. 80.
    Chung CD, Patel VP, Moran M, Lewis LA, Miceli MC. Galectin-1 induces partial TCR -chain phosphorylation and antagonizes processive TCR signal transduction. J Immunol. 2000;165(7):3722–9.PubMedGoogle Scholar
  81. 81.
    Sano H, Hsu DK, Yu L, Apgar JR, Kuwabara I, Yamanaka T, et al. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol. 2000;165(4):2156–64.PubMedGoogle Scholar
  82. 82.
    Rao SP, Ge XN, Sriramarao P. Regulation of eosinophil recruitment and activation by galectins in allergic asthma. Front Med (Lausanne). 2017;4:68.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019
corrected publication 2019

Authors and Affiliations

  • Shigeharu Ueki
    • 1
    Email author
  • Yui Miyabe
    • 1
    • 2
  • Yohei Yamamoto
    • 3
  • Mineyo Fukuchi
    • 1
  • Makoto Hirokawa
    • 1
  • Lisa A. Spencer
    • 4
  • Peter F. Weller
    • 5
  1. 1.Department of General Internal Medicine and Clinical Laboratory MedicineAkita University Graduate School of MedicineAkitaJapan
  2. 2.Department of Otorhinolaryngology, Head & Neck SurgeryAkita University HospitalAkitaJapan
  3. 3.Department of Molecular Pathology and Tumor PathologyAkita University Graduate School of MedicineAkitaJapan
  4. 4.Department of PediatricsUniversity of Colorado School of MedicineDenverUSA
  5. 5.Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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