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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    Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360(10):985-993.

    Not in our library10.1056/nejmoa0805435

96. 96.

    Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651-659.

    Not in our library10.1016/s0140-6736(12)60988-x

97. 97.

    Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID, SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189-1197.

    Not in our library10.1056/nejmoa1403291

98. 98.

    Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P, Investigators MENSA. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-1207.

    Not in our library10.1056/nejmoa1403290

99. 99.

    Hom S, Pisano M. Reslizumab (Cinqair): an Interleukin-5 antagonist for severe asthma of the eosinophilic phenotype. P T. 2017;42(9):564-568.

    Not in our library

100. 100.

     Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Wilkins HJ, Henkel T, Nair P. Res-5-0010 study group. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184(10):1125-1132.

     Not in our library10.1164/rccm.201103-0396oc

101. 101.

     Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O’Brien C, Korn S. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3(5):355-366.

     Not in our library10.1016/s2213-2600(15)00042-9

102. 102.

     Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 study of Reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest. 2016;150(4):799-810.

     Not in our library10.1016/j.chest.2016.03.018

103. 103.

     Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132(5):1086-1096.e5.

     Not in our library10.1016/j.jaci.2013.05.020

104. 104.

     Hilvering B, Xue L, Pavord ID. Evidence for the efficacy and safety of anti-interleukin-5 treatment in the management of refractory eosinophilic asthma. Ther Adv Respir Dis. 2015;9(4):135-145.

     Not in our library10.1177/1753465815581279

105. 105.

     Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall’acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344-1353.e2.

     Not in our library10.1016/j.jaci.2010.04.004

106. 106.

     Nowak RM, Parker JM, Silverman RA, Rowe BH, Smithline H, Khan F, Fiening JP, Kim K, Molfino NA. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am J Emerg Med. 2015;33(1):14-20.

     Not in our library10.1016/j.ajem.2014.09.036

107. 107.

     Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, Gossage DL, Ward CK, Wu Y, Wang B, Khatry DB, van der Merwe R, Kolbeck R, Molfino NA, Raible DG. Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014;2(11):879-890.

     Not in our library10.1016/s2213-2600(14)70201-2

108. 108.

     FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, Gilmartin G, Werkström V, Aurivillius M, Goldman M, study investigators CALIMA. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141.

     Not in our library10.1016/s0140-6736(16)31322-8

109. 109.

     Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkström V, Goldman M, SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β₂−agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127.

     Not in our library10.1016/s0140-6736(16)31324-1

110. 110.

     Hart TK, Blackburn MN, Brigham-Burke M, Dede K, Al-Mahdi N, Zia-Amirhosseini P, Cook RM. Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol. 2002;130(1):93-100.

     Not in our library10.1046/j.1365-2249.2002.01973.x

111. 111.

     Slager RE, Otulana BA, Hawkins GA, Yen YP, Peters SP, Wenzel SE, Meyers DA, Bleecker ER. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist. J Allergy Clin Immunol. 2012;130(2):516-22.e4.

     Not in our library10.1016/j.jaci.2012.03.030

112. 112.

     Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455-2466.

     Not in our library10.1056/nejmoa1304048

113. 113.

     Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Sutherland ER, Evans RR, Joish VN, Eckert L, Graham NM, Stahl N, Yancopoulos GD, Louis-Tisserand M, Teper A. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388(10039):31-44.

     Not in our library10.1016/s0140-6736(16)30307-5

114. 114.

     Hua F, Ribbing J, Reinisch W, Cataldi F, Martin S. A pharmacokinetic comparison of anrukinzumab, an anti- IL-13 monoclonal antibody, among healthy volunteers, asthma and ulcerative colitis patients. Br J Clin Pharmacol. 2015;80(1):101-109.

     Not in our library10.1111/bcp.12589

115. 115.

     Hanania NA, Noonan M, Corren J, Korenblat P, Zheng Y, Fischer SK, Cheu M, Putnam WS, Murray E, Scheerens H, Holweg CT, Maciuca R, Gray S, Doyle R, McClintock D, Olsson J, Matthews JG, Yen K. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax. 2015;70(8):748-756.

     Not in our library10.1136/thoraxjnl-2014-206719

116. 116.

     Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, Harris JM, Scheerens H, Wu LC, Su Z, Mosesova S, Eisner MD, Bohen SP, Matthews JG. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088-1098.

     Not in our library10.1056/nejmoa1106469

117. 117.

     Scheerens H, Arron JR, Zheng Y, Putnam WS, Erickson RW, Choy DF, Harris JM, Lee J, Jarjour NN, Matthews JG. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin Exp Allergy. 2014;44(1):38-46.

     Not in our library10.1111/cea.12220

118. 118.

     Noonan M, Korenblat P, Mosesova S, Scheerens H, Arron JR, Zheng Y, Putnam WS, Parsey MV, Bohen SP, Matthews JG. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J Allergy Clin Immunol. 2013;132(3):567-574.

     Not in our library10.1016/j.jaci.2013.03.051

119. 119.

     Brightling CE, Chanez P, Leigh R, O’Byrne PM, Korn S, She D, May RD, Streicher K, Ranade K, Piper E. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3(9):6.

     Not in our library10.1016/s2213-2600(15)00197-6

120. 120.

     Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, She D, Kell C, May RD, Geba GP, Molfino NA. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41(2):330-338.

     Not in our library10.1183/09031936.00223411

121. 121.

     Parker JM, Glaspole IN, Lancaster LH, Haddad TJ, She D, Roseti SL, Fiening JP, Grant EP, Kell CM, Flaherty KR. A Phase 2 randomized controlled study of Tralokinumab in subjects with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2018;197:94-103.

     Not in our library10.1164/rccm.201704-0784oc

122. 122.

     Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, van der Merwe R. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377(10):936-946.

     Not in our library10.1056/nejmoa1704064

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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