The modern view of the role of innate and adaptive immunity in bronchial asthma

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This article provides an overview of international data about immunological aspects of the pathophysiology of bronchial asthma (BA). The relationship between innate and adaptive immunity, as well as participation of various interleukins and cells in the development of inflammation in BA are presented. The possibility of the creation of new therapeutic molecules for the treatment of BA is substantiated.

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M A Galitskaya

NRC Institute of Immunology FMBA of Russia


O M Kurbacheva

NRC Institute of Immunology FMBA of Russia

  1. Global Initiative for Asthma. Global Strategy for AsthmaManagement and Prevention (2016 update). GINA. 2016. www (Ссылка активна на 14.04.2017 г.).
  2. Федеральные клинические рекомендации по диагностике и лечению бронхиальной астмы. 2016. www.pulmonology. ru. (Ссылка активна на 06.09.2017 г.).
  3. Национальная программа «Бронхиальная астма у детей. Стратегия лечения и профилактика». 2012 (IV издание).
  4. Domingo C., Pacheco A., Hinojosa M., Bosque M. The relevanceof IgE in the pathogenesis of allergy: the effect of an anti-IgE drug in asthma and other diseases. Recent Pat Inflamm Allergy Drug Discov. 2007;1:151-164. doi: 10.2174/187221307780979865.
  5. Boyman O., Kaegi C., Akdis M., Bavbek S., Bossios A., Chatzipetrou A. et al. EAACI IG Biologicals taskforce paper on the use ofbiologic agents in allergic disorders. Allergy. 2015;(70):727-754. doi: 10.1111/all.12616.
  6. Domingo C. Omalizumab for severe asthma: efficacy beyond the atopic patient? Drugs. 2014;74:521-533. DOI: 10.1007/ s40265-014-0203-y.
  7. Kumar S., Hedges SB. A molecular time scale for vertebrate evolution. Nature. 1998;(392):917-920. doi: 10.1038/31927.
  8. Warr GW, Magor KE, Higgins DA. IgY clues to the origins of modern antibodies. Immunol Today. 1995;16:392-398. doi: 10.1016/0167-5699(95)80008-5.
  9. Achatz G., Lamers M., Crameri R. Membrane Bound IgE: the key receptor to restrict high IgE levels. Open Immunol J. 2008;1:25-32. doi: 10.2174/1874226200801010025.
  10. Hammad H., Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol. 2008;8:193-204. doi: 10.1038/nri2275.
  11. Pearce N., Pekkanen J., Beasley R. How much asthma is really attributable to atopy? Thorax. 1999;54:268-272. doi: 10.1136/thx.54.3.268.
  12. Domingo C. Overlapping effects of new monoclonal antibodies for severe asthma. Drugs. 2017;77:1769-1787. DOI: 10.1007/ s40265-017-0810-5.
  13. Le H., Kim W., Kim J., Cho HR, Kwon B. Interleukin-33: a mediator of inflammation targeting hematopoietic stem and progenitor cells and their progenies. Front Immunol. 2013;4:104. doi: 10.3389/fimmu.2013.00104.
  14. Matucci A., Vultaggio A., Maggi E., Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respiratory Research. 2018;19:1-10. doi: 10.1186/s12931-018-0813-0.
  15. Brusselle GG, Maes T., Bracke KR. Eosinophils in the spotlight: Eosinophilic airway inflammation in nonallergic asthma. Nature Med. 2013;19:977-979. doi: 10.1038/nm.3300.
  16. Pelly VS, Kannan Y., Coomes SM, Entwistle LJ, Ruückerl D., Seddon B. et al. IL-4-producing ILC2 are required for the differentiation of T(H)2cells following Heligmosomoides polygyrus infection. Mucosal Immunol. 2016;9:1407-1417. doi: 10.1038/mi.2016.4.
  17. Lund S., Walford HH, Doherty TA. Type 2 innate lymphoid cells in allergic disease. Curr Immunol Rev. 2014;9:214-221. doi: 10.2174/1573395510666140304235916.
  18. Oliphant CJ, Hwang YY, Walker JA, Salimi M., Wong SH, Brewer JM et al. MHC II-mediated dialog between group 2 innate lymphoid cells and CD4+ T-cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity. 2014;41:283-295. doi: 10.1016/j.immuni.2014.06.016.
  19. Coyle AJ, Le Gros G., Bertrand C., Tsuyuki S., Heusser CH, Kopf M. et al. Interleukin-4 is required for the induction of lung Th2 mucosal immunity. Am J. Respir Cell Mol Biol. 1995;13:54-59. doi: 10.1165/ajrcmb.13.1.7598937.
  20. Cohn L., Homer RJ, Mac Leod H., Mohrs M., Brombacher F., Bottomly K. Th2-induced airway mucus production is dependenton IL-4Ralpha, but not on eosinophils. J. Immunol. 1999;162:6178-6183.
  21. Kolbeck R., Kozhich A., Koike M., Peng L., Andersson CK, Damschroder MM et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J. Allergy Clin Immunol. 2010;125:1344-1353. doi: 10.1016/j.jaci.2010.04.004.
  22. Rothenberg ME. Eosinophilia. N. Engl J. Med. 1998;338:1592-1600. doi: 10.1056/nejm199805283382206.
  23. Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J. Exp Med. 1988;167:219-224. doi: 10.1084/jem.167.1.219.
  24. Rosenberg HF, Phipps S., Foster PS. Eosinophil trafficking in allergy and asthma. J. Allergy Clin Immunol. 2007;119:1303-1312. doi: 10.1016/j.jaci.2007.03.048.
  25. Pelaia G., Vatrella A., Busceti MT, Gallelli L., Preianô M., Lombardo N. et al. Role of biologics in severe eosinophilic asthma - focus on reslizumab. Ther Clin Risk Manag. 2016;12:1075-1082. doi: 10.2147/tcrm.s111862.
  26. Kurowska-Stolarska M., Stolarski B., Kewin P., Murphy G., Corrigan CJ, Ying S. et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J. Immunol. 2009;183:6469-6477. doi: 10.4049/jimmunol.0901575.
  27. Pastorelli L., Garg RR, Hoang SB, Spina L., Mattioli B., Scarpa M. et al. Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th 1/Th2 driven enteritis. Proc Natl Acad Sci USA. 2010;107:8017-8022. doi: 10.1073/pnas.0912678107.
  28. Wills-Karp M., Rani R., Dienger K., Lewkowich I., Fox JG, Perkins C. et al. Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection. J. Exp Med. 2012;209:607-622. doi: 10.1084/jem.20110079.
  29. Guo L., Wei G., Zhu J., Liao W., Leonard WJ, Zhao Ket al. IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1-cells. Proc Natl Acad Sci USA. 2009;106:13463-13468. doi: 10.1073/pnas.0906988106.
  30. Besnard AG, Togbe D., Guillou N., Erard F., Quesniaux V., Ryffel B. IL-33-activated dendritic cells are critical for allergic airway inflammation. Eur J. Immunol. 2011;41:1675-1686. doi: 10.1002/eji.201041033.
  31. Rank MA, Kobayashi T., Kozaki H., Bartemes KR, Squillace DL, Kita H. IL-33-activated dendritic cells induce an atypical TH2-type response. J. Allergy Clin Immunol. 2009;123:1047-1054. doi: 10.1016/j.jaci.2009.02.026.
  32. Arshad MI, Khan HA, Noel G., Piquet-Pellorce C., Samson M. Potential therapeutic aspects of alarmin cytokine interleukin 33 or its inhibitors in various diseases. Clin Ther. 2016;38:1000-1016. doi: 10.1016/j.clinthera.2016.02.021.
  33. Smithgall MD, Comeau MR, Yoon BR, Kaufman D., Armitage R., Smith De. IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2cells, iNKT and NK cells. Int Immunol. 2008;20:1019-1030. doi: 10.1093/intimm/dxn060.
  34. Yagami A., Orihara K., Morita H., Futamura K., Hashimoto N., Matsumoto K. et al. IL-33 mediates inflammatory responses in human lung tissue cells. J. Immunol. 2010;185:5743-5750. doi: 10.4049/jimmunol.0903818.
  35. Newcomb DC, Peebles RS. Th17-mediated inflammation in asthma. Curr Opin Immunol. 2013;25:755-760. doi: 10.1016/j.coi.2013.08.002.
  36. Jartti J., Jerne JE. Role of viral infections in the development and exacerbation of asthma in children. J. Allergy Clin Immunol. 2017;140:895-906. doi: 10.1016/j.jaci.2017.08.003.
  37. Openshaw PJ, Tregonin JS. Immune responses and disease enhancement during respiratory syncytial virus infection. Clin Microbiol Rev. 2005;18:541-555. doi: 10.1128/cmr.18.3.541-555.2005.
  38. Schwantes EA, Manthei DM, Denlinger LC, Evans MD, Gern JE, Jarjour NN et al. Interferon gene expression in sputum cells correlates with the Asthma Index Score during virus-induced exacerbations. Clin Exp Allergy. 2014;44:813-821. doi: 10.1111/cea.12269.
  39. Vultaggio A., Nencini F., Pratesi S., Petroni G., Romagnani S., Maggi E. Poly (I:C) promotes the production of IL-17A by murine CD1d-driven invariant NKT cells in airway inflammation. Allergy. 2012;67:1223-1232. doi: 10.1111/j.1398-9995.2012.02876.x.
  40. Fajt ML, Wenzel SE. Biologic therapy in asthma: entering the new age of personalized medicine. J. Asthma. 2014;51:669-676. doi: 10.3109/02770903.2014.910221.
  41. Paul WE, Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429-459. doi: 10.1146/annurev. iy. 05.040187.002241.
  42. Thornhill MH, Kyan-Aung U., Haskard DO. IL-4 increases human endothelial cell adhesiveness for T-cells but not for neutrophils. J. Immunol. 1990;144:3060-3065.
  43. Masinovsky B., Urdal D., Gallatin WM. IL-4 acts synergistically with IL-1 beta to promote lymphocyte adhesion to micro-vascular endothelium by induction of vascular cell adhesion molecule-1. J. Immunol. 1990;145:2886-2895.
  44. Chang JE, Doherty TA, Baum R., Broide D. Prostaglandin D2 regulates human type 2 innate lymphoid cell chemotaxis. J. Allergy ClinImmunol. 2014;133:899-901. DOI: 10.1016/j. jaci.2013.09.020.
  45. Briscoe DM, Cotran RS, Pober JS. Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo. Correlation with CD3+ T-cell infiltration. J. Immunol. 1992;149:2954-2960.
  46. Kroeger KM, Sullivan BM, Locksley RM. IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38al-pha-dependent pathway. J. Leukoc Biol. 2009;86:769-778. doi: 10.1189/jlb.0708452.
  47. Mentink-Kane MM, Wynn TA. Opposing roles for IL-13 and IL-13 receptor alpha 2 in health and disease. Immunol Rev. 2004;202:191-202. doi: 10.1111/j.0105-2896.2004.00210.x.
  48. McKenzie GJ, Emson CL, Bell SE, Anderson S., Fallon P., Zurawski G. et al. Impaired development of Th2-cells in IL-13-deficient mice. Immunity. 1998;9:423-432. doi: 10.1016/s1074-7613(00)80625-1.
  49. Halim TE, Steer CA, Mathaü L., Gold MJ, Martinez-Gonzalez I., McNagny KM et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T-helper 2 cell-mediated allergic lung inflammation. Immunity. 2014;40:425-435. doi: 10.1016/j.immuni.2014.01.011.
  50. Mesnil C., Raulier S., Paulissen G., Xiao X., Birrell MA, Pirottin D. et al. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J. Clin Invest. 2016;126:3279-3295. doi: 10.1172/jci85664.
  51. Wadsworth S., Sin D., Dorscheid D. Clinical update on the use of biomarkers of airway inflammation in the management of asthma. J. Asthma Allergy. 2011;4:77-86. doi: 10.2147/jaa. s15081.
  52. Walsh GM. An update on emerging drugs for asthma. Expert Opin Emerg Drugs. 2012;17:37-42. doi: 10.1517/14728214.2012.657625.
  53. Hogan SP, Rosenberg HF, Moqbel R., Phipps S., Foster PS, Lacy P. et al. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. 2008;38:709-750. doi: 10.1111/j.1365-2222.2008.02958.x.
  54. Bousquet J., Chanez P., Lacoste JY, Barneon G., Ghavanian N., Enander I. et al. Eosinophilic inflammation in asthma. N. Engl J. Med. 1990;323:1033-1039. DOI: 10.1056/ nejm199010113231505.
  55. Flood-Page P., Swenson C., Faiferman I., Matthews J., Williams M., Brannick L. et al. International Mepolizumab Study Group. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J. Respir Crit Care Med. 2007;176:1062-1071. DOI: 10.1164/ rccm.200701-085oc.
  56. Moqbel R., Ying S., Barkans J., Newman TM, Kimmitt P., Wakelin M. et al. Identification of messenger RNA for IL-4 in human eosinophils with granule localization and release of the translated product. J. Immunol. 1995;155:4939-4947.
  57. Nakajima H., Gleich GJ, Kita H. Constitutive production of IL-4 and IL-10 and stimulated production of IL-8 by normal peripheral blood eosinophils. J. Immunol. 1996;156:4859-4866.
  58. Nonaka M., Nonaka R., Woolley K., Adelroth E., Miura K., Okhawara Y. et al. Distinct immune histochemical localization of IL-4 inhuman inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils. J. Immunol. 1995;155:3234-3244.
  59. Chu VT, Froühlich A., Steinhauser G., Scheel T., Roch T., Fillatreau S. et al. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol. 2011;12:151-159. doi: 10.1038/ni.1981.
  60. Farhan RK, Vickers MA, Ghaemmaghami AM, Hall AM, Barker RN, Walsh GM. Effective antigen presentation to helper T-cells by human eosinophils. Immunology. 2016;149:413-422. doi: 10.1111/imm.12658.
  61. Shi HZ, Humbles A., Gerard C., Jin Z., Weller PF. Lymph node trafficking and antigen presentation by endobronchial eosinophils. J. Clin Invest. 2000;105:945-953. doi: 10.1172/jci8945.
  62. Akuthota P., Wang H., Weller PF. Eosinophils as antigen-presenting cells in allergic upper airway disease. Curr Opin Allergy Clin Immunol. 2010;10:14-19. DOI: 10.1097/ aci.0b013e328334f693.
  63. Lucey DR, Nicholson-Weller A., Weller PF. Mature human eosinophils have the capacity to express HLA-DR. Proc Natl Acad Sci USA. 1989;86:1348-1351. DOI: 10.1073/ pnas.86.4.1348.
  64. Akuthota P., Wang HB, Spencer LA, Weller PF. Immuno regulatory roles of eosinophils: a new look at a familiar cell. Clin Exp Allergy. 2008;38:1254-1263. doi: 10.1111/j.1365-2222.2008.03037.x.
  65. Moqbel R., Lacy P. New concepts in effector functions of eosinophil cytokines. Clin Exp Allergy. 2008;30:1667-1671. doi: 10.1111/j.1365-2222.2000.00991.x.
  66. Iademarco MF, Barks JL, Dean DC. Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-alpha in cultured endothelial cells. J. Clin Invest. 1995;95:264-271. doi: 10.1172/jci117650.
  67. Taniguchi M., Harada M., Kojo S., Nakayama T., Wakao H. The regulatory role of Valpha14 NKT cells in innate and acquired immune response. Annu Rev Immunol. 2003;21:483-513. doi: 10.1146/annurev.immunol.21.120601.141057.
  68. Akbari O., Stock P., Meyer E., Kronenberg M., Sidobre S., Nakayama T. et al. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med. 2003;9:582-588. DOI: 10.1038/ nm851.
  69. Meyer EH, Goya S., Akbari O., Berry GJ, Savage PB, Kronenberg M. et al. Glycolipid activation of invariant T-cell receptor+ NK T-cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T-cells. Proc Natl Acad Sci USA. 2006;103:2782-2787. doi: 10.1073/pnas.0510282103.
  70. Nagata Y., Kamijuku H., Taniguchi M., Ziegler S., Seino K. Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T. cell function. Int Arch Allergy Immunol. 2007;144:305-314. doi: 10.1159/000106319.
  71. Soumelis V., Reche PA, Kanzler H., Yuan W., Edward G., Homey B. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002;3:673-680. doi: 10.1038/ni805.
  72. Walter DM, McIntire JJ, Berry G., McKenzie AN, Donaldson DD, DeKruyff RH et al. Critical role for IL-13 in the development of allergen-induced airway hyperreactivity. J. Immunol. 2001;167:4668-4675. doi: 10.4049/jimmunol.167.8.4668.
  73. Wang YH, Ito T., Wang YH, Homey B., Watanabe N., Martin R. et al. Maintenance and polarization of human TH2 central memory T-cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity. 2006;24:827-838. DOI: 10.1016/j. immuni.2006.03.019.
  74. Beutler B. Innate immunity: an overview. Mol Immunol. 2004;40:845-859. doi: 10.1016/j.molimm.2003.10.005.
  75. Ebner S., Nguyen VA, Forstner M., Wang YH, Wolfram D., Liu YJ et al. Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T-cells. J. Allergy Clin Immunol. 2007;119:982-990. doi: 10.1016/j.jaci.2007.01.003.
  76. Liu YJ. Thymic stromal lymphopoietin: master switch for allergic inflammation. J. Exp Med. 2006;203:269-273. doi: 10.1084/jem.20051745.
  77. Ying S., O’Connor B., Ratoff J., Meng Q., Mallett K., Cousins D. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 2005;174:8183-8190. doi: 10.4049/jimmunol.174.12.8183.
  78. Zhou B., Comeau MR, De Smedt T., Liggitt HD, Dahl ME, Lewis DB et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol. 2005;6:1047-1053. doi: 10.1038/ni1247.
  79. Liu YJ. TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol. 2009;101:1-25. doi: 10.1016/s0065-2776(08)01001-8.
  80. Allakhverdi Z., Smith DE, Comeau MR, Delespesse G. Cuttingedge: the ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J. Immunol. 2007;179:2051-2054. doi: 10.4049/jimmunol.179.4.2051.
  81. Pelaia G., Vatrella A., Maselli R. The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012;11:958-972. doi: 10.1038/nrd3792.
  82. Peters SP, Busse WW. New and Anticipated Therapies for Severe Asthma. J. Allergy Clin Immunol Pract. 2017;5:15-24. doi: 10.1016/j.jaip.2017.07.008.
  83. Fajt ML, Gelhaus SL, Freeman B., Uvalle CE, Trudeau JB, Holguin F., Wenzel SE. Prostaglandin D2 pathway upregulation: relation to asthma severity, control, and TH2 inflammation. J. Allergy Clin Immunol. 2013;131:1504-1512. doi: 10.1016/j.jaci.2013.01.035.


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