Regulation of Eosinophilia in Asthma-New Therapeutic Approaches for Asthma Treatment

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Apr 30

PMID 33917396

Citations 9

Authors

Ruth P Cusack

Christiane E Whetstone

Yanqing Xie

Maral Ranjbar

Gail M Gauvreau

Affiliations

Soon will be listed here.

Abstract

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

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References

Toki S, Goleniewska K, Zhang J, Zhou W, Newcomb D, Zhou B . TSLP and IL-33 reciprocally promote each other's lung protein expression and ILC2 receptor expression to enhance innate type-2 airway inflammation. Allergy. 2020; 75(7):1606-1617. PMC: 7354889. DOI: 10.1111/all.14196. View

Ponath P, Qin S, Ringler D, Clark-Lewis I, Wang J, Kassam N . Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest. 1996; 97(3):604-12. PMC: 507095. DOI: 10.1172/JCI118456. View

Spencer L, Bonjour K, Melo R, Weller P . Eosinophil secretion of granule-derived cytokines. Front Immunol. 2014; 5:496. PMC: 4209865. DOI: 10.3389/fimmu.2014.00496. View

Soumelis V, Reche P, Kanzler H, Yuan W, Edward G, Homey B . Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002; 3(7):673-80. DOI: 10.1038/ni805. View

Guida L, OHehir R, Hawrylowicz C . Synergy between dexamethasone and interleukin-5 for the induction of major histocompatibility complex class II expression by human peripheral blood eosinophils. Blood. 1994; 84(8):2733-40. View

Nakamura Y, Ghaffar O, Olivenstein R, Taha R, Zhang D, Ray A . Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol. 1999; 103(2 Pt 1):215-22. DOI: 10.1016/s0091-6749(99)70493-8. View

Neill D, Wong S, Bellosi A, Flynn R, Daly M, Langford T . Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010; 464(7293):1367-70. PMC: 2862165. DOI: 10.1038/nature08900. View

Kalayci O, Sonna L, Woodruff P, Camargo Jr C, Luster A, Lilly C . Monocyte chemotactic protein-4 (MCP-4; CCL-13): a biomarker of asthma. J Asthma. 2004; 41(1):27-33. DOI: 10.1081/jas-120024590. View

Krug N, Hohlfeld J, Kirsten A, Kornmann O, Beeh K, Kappeler D . Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med. 2015; 372(21):1987-95. DOI: 10.1056/NEJMoa1411776. View

10.

Shen Z, Malter J . Determinants of eosinophil survival and apoptotic cell death. Apoptosis. 2015; 20(2):224-34. PMC: 5798882. DOI: 10.1007/s10495-014-1072-2. View

11.

Donnelly L, Barnes P . Defective phagocytosis in airways disease. Chest. 2012; 141(4):1055-1062. DOI: 10.1378/chest.11-2348. View

12.

Liu F, Goodarzi H, Chen H . IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011; 41(3):298-310. DOI: 10.1007/s12016-011-8252-4. View

13.

Kupczyk M, Haque S, Middelveld R, Dahlen B, Dahlen S . Phenotypic predictors of response to oral glucocorticosteroids in severe asthma. Respir Med. 2013; 107(10):1521-30. DOI: 10.1016/j.rmed.2013.07.014. View

14.

Rogliani P, Ritondo B, Puxeddu E, Pane G, Cazzola M, Calzetta L . Experimental Glucocorticoid Receptor Agonists for the Treatment of Asthma: A Systematic Review. J Exp Pharmacol. 2020; 12:233-254. PMC: 7495344. DOI: 10.2147/JEP.S237480. View

15.

Brightling C, Gaga M, Inoue H, Li J, Maspero J, Wenzel S . Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials. Lancet Respir Med. 2020; 9(1):43-56. DOI: 10.1016/S2213-2600(20)30412-4. View

16.

TOWNSEND J, Fallon G, Matthews J, Smith P, Jolin E, McKenzie N . IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity. 2000; 13(4):573-83. DOI: 10.1016/s1074-7613(00)00056-x. View

17.

Shaw J, Fakhri S, Citardi M, Porter P, Corry D, Kheradmand F . IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps. Am J Respir Crit Care Med. 2013; 188(4):432-9. PMC: 5448506. DOI: 10.1164/rccm.201212-2227OC. View

18.

Salimi M, Barlow J, Saunders S, Xue L, Gutowska-Owsiak D, Wang X . A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med. 2013; 210(13):2939-50. PMC: 3865470. DOI: 10.1084/jem.20130351. View

19.

Wenzel S, Wilbraham D, Fuller R, Burmeister Getz E, Longphre M . Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet. 2007; 370(9596):1422-31. DOI: 10.1016/S0140-6736(07)61600-6. View

20.

Chen R, Smith S, Salter B, El-Gammal A, Oliveria J, Obminski C . Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma. Am J Respir Crit Care Med. 2017; 196(6):700-712. DOI: 10.1164/rccm.201612-2427OC. View