Type 2 immunity in asthma

Abstract

Type 2-immunity represents the typical adaptive response to allergen exposure in atopic individuals. It mainly involves Th2 cells and immunoglobulin E, as the main orchestrators of type 2-inflammation. Recently, it has been highlighted that allergens may be responsible for a Th2 response beside specific IgE activation and that a number of other environmental stimuli, such as viruses and pollutants, can trigger the same pattern of inflammation beyond atopy. Emerging data sustain a substantial role of the so-called epithelial dysfunction in asthma pathogenesis, both from anatomic and functional point of view. Furthermore an increasing amount of evidence demonstrates the relevance of innate immunity in polarizing a Th2 impaired response in asthmatic patients. Under this perspective, the complex cross-talking between airway epithelium, innate and adaptive immunity is emerging as a major determinant of type 2-inflammation beyond allergens. This review will include an update on the relevance of dysregulation of innate and adaptive type 2-immunity in asthma pathogenesis, particularly severe asthma, and on the role of the allergens that are associated with severe asthma. Type 2-immunity also will be reviewed in the light of the current and upcoming targeted treatments for severe asthma.

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References 122

1. 1.

   Oliphant CJ, Barlow JL, McKenzie AN. Insights into the initiation of type 2 immune responses. Immunology. 2011;134(4):378-385.

   Not in our library10.1111/j.1365-2567.2011.03499.x

2. 2.

   Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol. 2015;15(5):271-282.

   Not in our library10.1038/nri3831

3. 3.

   Fahy JV. Type 2 inflammation in asthma—present in most, absent in many. Nat Rev Immunol. 2015;15(1):57-65.

   Not in our library10.1038/nri3786

4. 4.

   Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779-788.

   Not in our library10.1172/jci5909

5. 5.

   Finkelman FD, Urban JF. The other side of the coin: the protective role of the Th2 cytokines. J Allergy Clin Immunol. 2001;107(5):772-780.

   Not in our library10.1067/mai.2001.114989

6. 6.

   Berger A. Th1 and Th2 responses: what are they? BMJ. 2000;321(7258):424.

   Not in our library10.1136/bmj.321.7258.424

7. 7.

   Kubo M. Innate and adaptive type 2 immunity in lung allergic inflammation. Immunol Rev. 2017;278(1):162-172.

   Not in our library10.1111/imr.12557

8. 8.

   Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445-489.

   Not in our library10.1146/annurev-immunol-030409-101212

9. 9.

   Harada Y, Tanaka S, Motomura Y, et al. The 3′ enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity. 2012;36:188-200.

   Not in our library10.1016/j.immuni.2012.02.002

10. 10.

    Ballesteros-Tato A, Randall TD, Lund FE, Spolski R, Leonard WJ, León B. T follicular helper cell plasticity shapes pathogenic T helper 2 cell-mediated immunity to inhaled house dust mite. Immunity. 2016;44(2):259-273.

    Not in our library10.1016/j.immuni.2015.11.017

11. 11.

    Sawaguchi M, Tanaka S, Nakatani Y, et al. Role of mast cells and Ba-sophils in IgE responses and in allergic airway hyperresponsiveness. J Immunol. 2012;188:1809-1818.

    Not in our library10.4049/jimmunol.1101746

12. 12.

    Siracusa MC, Kim BS, Spergel JM, Artis D. Basophils and allergic inflammation. J Allergy Clin Immunol. 2013;132:789-801.

    Not in our library10.1016/j.jaci.2013.07.046

13. 13.

    Egawa M, Mukai K, Yoshikawa S, et al. Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4. Immunity. 2013;38:570-580.

    Not in our library10.1016/j.immuni.2012.11.014

14. 14.

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

    Not in our library10.1111/sji.12448

15. 15.

    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.

    Not in our library10.3389/fmed.2017.00139

16. 16.

    Yasukawa A, Hosoki K, Toda M, Miyake Y, Matsushima Y, Matsumoto T, Boveda-Ruiz D, Gil-Bernabe P, Nagao M, Sugimoto M, Hiraguchi Y, Tokuda R, Naito M, Takagi T, D’Alessandro-Gabazza CN, Suga S, Kobayashi T, Fujisawa T, Taguchi O, Gabazza EC. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells. PLoS One. 2013;8(5):e64281.

    Not in our library10.1371/journal.pone.0064281

17. 17.

    Holgate ST. The sentinel role of the airway epithelium in asthma pathogenesis. Immunol Rev. 2011;242(1):205-219.

    Not in our library10.1111/j.1600-065x.2011.01030.x

18. 18.

    Trian T, Allard B, Dupin I, Carvalho G, Ousova O, Maurat E, et al. House dust mites induce proliferation of severe asthmatic smooth muscle cells via an epithelium-dependent pathway. Am J Respir Crit Care Med. 2015;191(5):538-546.

    Not in our library10.1164/rccm.201409-1582oc

19. 19.
    Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms · 2015

    No notice
20. 20.

    Georas SN, Rezaee F. Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol. 2014;134(3):509-520.

    Not in our library10.1016/j.jaci.2014.05.049

21. 21.

    Lloyd CM, Saglani S. Epithelial cytokines and pulmonary allergic inflammation. Curr Opin Immunol. 2015;34:52-58.

    Not in our library10.1016/j.coi.2015.02.001

22. 22.

    Gon Y, Hashimoto S. Role of airway epithelial barrier dysfunction in pathogenesis of asthma. Allergol Int. 2018;67:12–17.

    Not in our library10.1016/j.alit.2017.08.011

23. 23.

    Loffredo LF, Abdala-Valencia H, Anekalla KR, Cuervo-Pardo L, Gottardi CJ, Berdnikovs S. Beyond epithelial-to-mesenchymal transition: common suppression of differentiation programs underlies epithelial barrier dysfunction in mild, moderate, and severe asthma. Allergy. 2017;72:1988–2004.

    Not in our library10.1111/all.13222

24. 24.

    Aghapour M, Raee P, Moghaddam SJ, Hiemstra PS, Heijink IH. Airway epithelial barrier dysfunction in COPD: role of cigarette smoke exposure. 2018;58:157–69

    Not in our library10.1165/rcmb.2017-0200tr

25. 25.

    Fedorov IA, Wilson SJ, Davies DE, Holgate ST. Epithelial stress and structural remodel- ling in childhood asthma. Thorax. 2005;60:389-394.

    Not in our library10.1136/thx.2004.030262

26. 26.

    Jackson DJ, Makrinioti H, Rana BM, Shamji BW, Trujillo-Torralbo MB, Footitt J, Del-Rosario J, Telcian AG, Nikonova A, Zhu J, Aniscenko J, Gogsadze L, Bakhsoliani E, Traub S, Dhariwal J, Porter J, Hunt D, Hunt T, Hunt T, Stanciu LA, Khaitov M, Bartlett NW, Edwards MR, Kon OM, Mallia P, Papadopoulos NG, Akdis CA, Westwick J, Edwards MJ, Cousins DJ, Walton RP, Johnston SL. IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo. Am J Respir Crit Care Med. 2014;190(12):1373-1382.

    Not in our library10.1164/rccm.201406-1039oc

27. 27.

    Beale J, Jayaraman A, Jackson DJ, Macintyre JDR, Edwards MR, Walton RP, Zhu J, Man Ching Y, Shamji B, Edwards M, Westwick J, Cousins DJ, Yi Hwang Y, McKenzie A, Johnston SL, Bartlett NW. Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation. Sci Transl Med. 2014;6(256):256ra134.

    Not in our library10.1126/scitranslmed.3009124

28. 28.

    Bosco A, Ehteshami S, Stern DA, Martinez FD. Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction. Mucosal Immunol. 2010;3:399-409.

    Not in our library10.1038/mi.2010.13

29. 29.

    Han H, Roan F, Ziegler SF. The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines. Immunol Rev. 2017;278(1):116-130.

    Not in our library10.1111/imr.12546

30. 30.

    Omhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and thera- peutic opportunities. Antioxid Redox Signal. 2010;12:93-124.

    Not in our library10.1089/ars.2008.2425

31. 31.

    Boulet LP. Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Curr Opin Pulm Med. 2017; [Epub ahead of print]

    Not in our library10.1097/mcp.0000000000000441

32. 32.

    Loxham M, Davies DE. Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients. J Allergy Clin Immunol. 2017;139(6):1736-1751.

    Not in our library10.1016/j.jaci.2017.04.005

33. 33.
    Determinants of Divergent Adaptive Immune Responses after Airway Sensitization with Ligands of Toll-Like Receptor 5 or Toll-Like Receptor 9. · 2016

    Not checked
34. 34.

    Liu S, Verma M, Michalec L, Liu W, Sripada A, Rollins D, Good J, Ito Y, Chu H, Gorska MM, Martin RJ, Alam R. Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: the role of thymic stromal lymphopoietin. J Allergy Clin Immunol. 2018;141(1):257-268.e6.

    Not in our library10.1016/j.jaci.2017.03.032

35. 35.

    Hu Y, Dong H, Zou M, Huang C, Luo L, Yu C, Chen J, Xie Z, Zhao H, Le Y, Zou F, Liu L, Cai S. TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM-induced asthma model. Cell Immunol. 2017;315:56-63.

    Not in our library10.1016/j.cellimm.2017.02.003

36. 36.

    Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O’Byrne PM, Gauvreau GM, Boulet LP, Lemiere C, Martin J, Nair P, Sehmi R. 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(1):75-86.e8.

    Not in our library10.1016/j.jaci.2015.05.037

37. 37.

    Larose MC, Archambault AS, Provost V, Laviolette M, Flamand N. Regulation of eosinophil and group 2 innate lymphoid cell trafficking in asthma. Front Med (Lausanne). 2017;4:136.

    Not in our library10.3389/fmed.2017.00136

38. 38.

    Chen CC, Kobayashi T, Iijima K, Hsu FC, Kita H. IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs. J Allergy Clin Immunol. 2017;

    Not in our library10.1016/j.jaci.2017.01.015

39. 39.

    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(3):671-678.

    Not in our library10.1016/j.jaci.2014.06.024

40. 40.

    Tussiwand R, Everts B, Grajales-Reyes GE, et al. Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses. Immunity. 2015;42:916-928.

    Not in our library10.1016/j.immuni.2015.04.017

Cited by papers we hold 2

• Type 2 immunity in allergic diseases · 2025
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• PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite · 2021
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