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Group 2 Innate Lymphoid Cells and Asthma

  • Koichiro AsanoEmail author
Chapter
Part of the Respiratory Disease Series: Diagnostic Tools and Disease Managements book series (RDSDTDM)

Abstract

Group 2 innate lymphoid cells (ILC2s) do not express antigen-specific receptors or lineage-specific surface markers but produce large amounts of Th2 cytokines in response to interleukin (IL)-25 and IL-33 secreted from bronchial epithelial cells stimulated with protease-based allergens or infection with microorganisms. The number of ILC2s are increased and activated in the peripheral blood and airways of patients with asthma, especially with severe and/or eosinophilic forms. Corticosteroids can induce ILC2 apoptosis; however, these cells acquire corticosteroid resistance through activation of the Janus kinase/signal transducer and activator of transcription 5 pathway by thymic stromal lymphopoietin or IL-7. ILC2 activities are negatively regulated by interferons; however, lack of type I and III interferon synthesis in asthmatic airways exacerbates inflammation during respiratory viral infection.

Keywords

Interleukin-33 Thymic stromal lymphopoietin Corticosteroids Viral infection Interferon 

Notes

Acknowledgments

This research was supported by the Japan Agency for Medical Research and Development (AMED) under grant number JP18ek0410026.

References

  1. 1.
    Yoshimoto T, Matsushita K. Innate-type and acquired-type allergy regulated by IL-33. Allergol Int. 2014;63(Suppl 1):3–11.  https://doi.org/10.2332/allergolint.13-RA-0657.CrossRefPubMedGoogle Scholar
  2. 2.
    Bartemes KR, Kephart GM, Fox SJ, Kita H. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134:671–8.e4.  https://doi.org/10.1016/j.jaci.2014.06.024.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Jia Y, Fang X, Zhu X, Bai C, Zhu L, Jin M, et al. IL-13+ type 2 innate lymphoid cells correlate with asthma control status and treatment response. Am J Respir Cell Mol Biol. 2016;55:675–83.  https://doi.org/10.1165/rcmb.2016-0099OC.CrossRefPubMedGoogle Scholar
  4. 4.
    Liu T, Wu J, Zhao J, Wang J, Zhang Y, Liu L, et al. Type 2 innate lymphoid cells: a novel biomarker of eosinophilic airway inflammation in patients with mild to moderate asthma. Respir Med. 2015;109:1391–6.  https://doi.org/10.1016/j.rmed.2015.09.016.CrossRefPubMedGoogle Scholar
  5. 5.
    Nagakumar P, Denney L, Fleming L, Bush A, Lloyd CM, Saglani S. Type 2 innate lymphoid cells in induced sputum from children with severe asthma. J Allergy Clin Immunol. 2016;137:624.e6–6.e6.  https://doi.org/10.1016/j.jaci.2015.06.038.CrossRefGoogle Scholar
  6. 6.
    Christianson CA, Goplen NP, Zafar I, Irvin C, Good JT Jr, Rollins DR, et al. Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33. J Allergy Clin Immunol. 2015;136:59–68.e14.  https://doi.org/10.1016/j.jaci.2014.11.037.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O’Byrne PM, et al. Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol. 2016;137:75–86.e8.  https://doi.org/10.1016/j.jaci.2015.05.037.CrossRefPubMedGoogle Scholar
  8. 8.
    Rossios C, Pavlidis S, Hoda U, Kuo CH, Wiegman C, Russell K, et al. Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma. J Allergy Clin Immunol. 2017;141(2):560–70.  https://doi.org/10.1016/j.jaci.2017.02.045.CrossRefPubMedGoogle Scholar
  9. 9.
    Kabata H, Moro K, Fukunaga K, Suzuki Y, Miyata J, Masaki K, et al. Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat Commun. 2013;4:2675.  https://doi.org/10.1038/ncomms3675.CrossRefPubMedGoogle Scholar
  10. 10.
    Walford HH, Lund SJ, Baum RE, White AA, Bergeron CM, Husseman J, et al. Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness. Clin Immunol. 2014;155:126–35.  https://doi.org/10.1016/j.clim.2014.09.007.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Liu S, Verma M, Michalec L, Liu W, Sripada A, Rollins D, et al. Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin. J Allergy Clin Immunol. 2017;141(1):257–268.e6.  https://doi.org/10.1016/j.jaci.2017.03.032.CrossRefPubMedGoogle Scholar
  12. 12.
    Kumar RK, Foster PS, Rosenberg HF. Respiratory viral infection, epithelial cytokines, and innate lymphoid cells in asthma exacerbations. J Leukoc Biol. 2014;96:391–6.  https://doi.org/10.1189/jlb.3RI0314-129R.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Jackson DJ, Makrinioti H, Rana BM, Shamji BW, Trujillo-Torralbo MB, Footitt J, et al. IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo. Am J Respir Crit Care Med. 2014;190:1373–82.  https://doi.org/10.1164/rccm.201406-1039OC.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Byers DE, Alexander-Brett J, Patel AC, Agapov E, Dang-Vu G, Jin X, et al. Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease. J Clin Invest. 2013;123:3967–82.  https://doi.org/10.1172/JCI65570.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mohapatra A, Van Dyken SJ, Schneider C, Nussbaum JC, Liang HE, Locksley RM. Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis. Mucosal Immunol. 2016;9:275–86.  https://doi.org/10.1038/mi.2015.59.CrossRefPubMedGoogle Scholar
  16. 16.
    Qi F, Wang D, Liu J, Zeng S, Xu L, Hu H, et al. Respiratory macrophages and dendritic cells mediate respiratory syncytial virus-induced IL-33 production in TLR3- or TLR7-dependent manner. Int Immunopharmacol. 2015;29:408–15.  https://doi.org/10.1016/j.intimp.2015.10.022.CrossRefPubMedGoogle Scholar
  17. 17.
    Stier MT, Bloodworth MH, Toki S, Newcomb DC, Goleniewska K, Boyd KL, et al. Respiratory syncytial virus infection activates IL-13-producing group 2 innate lymphoid cells through thymic stromal lymphopoietin. J Allergy Clin Immunol. 2016;138:814–24.e11.  https://doi.org/10.1016/j.jaci.2016.01.050.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zeng S, Wu J, Liu J, Qi F, Liu B. IL-33 receptor (ST2) signalling is important for regulation of Th2-mediated airway inflammation in a murine model of acute respiratory syncytial virus infection. Scand J Immunol. 2015;81:494–501.  https://doi.org/10.1111/sji.12284.CrossRefPubMedGoogle Scholar
  19. 19.
    Han M, Hong JY, Jaipalli S, Rajput C, Lei J, Hinde JL, et al. IFN-gamma blocks development of an asthma phenotype in rhinovirus-infected baby mice by inhibiting type 2 innate lymphoid cells. Am J Respir Cell Mol Biol. 2017;56:242–51.  https://doi.org/10.1165/rcmb.2016-0056OC.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Werder RB, Zhang V, Lynch JP, Snape N, Upham JW, Spann K, et al. Chronic IL-33 expression predisposes to virus-induced asthma exacerbations by increasing type 2 inflammation and dampening antiviral immunity. J Allergy Clin Immunol. 2017;141(5):1607–1619.e9.  https://doi.org/10.1016/j.jaci.2017.07.051.CrossRefPubMedGoogle Scholar
  21. 21.
    Han M, Rajput C, Hong JY, Lei J, Hinde JL, Wu Q, et al. The innate cytokines IL-25, IL-33, and TSLP cooperate in the induction of type 2 innate lymphoid cell expansion and mucous metaplasia in rhinovirus-infected immature mice. J Immunol. 2017;199:1308–18.  https://doi.org/10.4049/jimmunol.1700216.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Moro K, Kabata H, Tanabe M, Koga S, Takeno N, Mochizuki M, et al. Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses. Nat Immunol. 2016;17:76–86.  https://doi.org/10.1038/ni.3309.CrossRefPubMedGoogle Scholar
  23. 23.
    Duerr CU, McCarthy CD, Mindt BC, Rubio M, Meli AP, Pothlichet J, et al. Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells. Nat Immunol. 2016;17:65–75.  https://doi.org/10.1038/ni.3308.CrossRefPubMedGoogle Scholar
  24. 24.
    Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, Kebadze T, Mallia P, Stanciu LA, Parker HL, et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12:1023–6.CrossRefGoogle Scholar
  25. 25.
    Durrani SR, Montville DJ, Pratt AS, Sahu S, DeVries MK, Rajamanickam V, et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol. 2012;130:489–95.  https://doi.org/10.1016/j.jaci.2012.05.023.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Tversky JR, Le TV, Bieneman AP, Chichester KL, Hamilton RG, Schroeder JT. Human blood dendritic cells from allergic subjects have impaired capacity to produce interferon-alpha via Toll-like receptor 9. Clin Exp Allergy. 2008;38:781–8.  https://doi.org/10.1111/j.1365-2222.2008.02954.x.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Wark PA, Johnston SL, Bucchieri F, Powell R, Puddicombe S, Laza-Stanca V, Holgate ST, Davies DE. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201:937–47.CrossRefGoogle Scholar
  28. 28.
    Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ Jr, Calatroni A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015;136:1476–85.  https://doi.org/10.1016/j.jaci.2015.09.008.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Djukanovic R, Harrison T, Johnston SL, Gabbay F, Wark P, Thomson NC, et al. The effect of inhaled IFN-beta on worsening of asthma symptoms caused by viral infections. A randomized trial. Am J Respir Crit Care Med. 2014;190:145–54.  https://doi.org/10.1164/rccm.201312-2235OC.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Division of Pulmonary Medicine, Department of MedicineTokai University School of MedicineKanagawaJapan

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