Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:142

Article

Toki, Shinji¹  Goleniewska, Kasia¹  Reiss, Sara¹  Zhang, Jian¹  Bloodworth, Melissa H.²  Stier, Matthew T.²  Zhou, Weisong¹  Newcomb, Dawn C.^1,2  Ware, Lorraine B.^1,2  Stanwood, Gregg D.^6,7  Galli, Aurelio^3,5  Boyd, Kelli L.²  Niswender, Kevin D.^3,4,5,8  Peebles, R. Stokes, Jr.^1,2,8 

[1] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA

[2] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA

[3] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA

[4] Vanderbilt Univ, Sch Med, Div Diabet Endocrinol & Metab, Nashville, TN 37212 USA

[5] Vanderbilt Univ, Sch Med, Vanderbilt Brain Inst, Nashville, TN 37212 USA

[6] Florida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 USA

[7] Florida State Univ, Ctr Brain Repair, Tallahassee, FL 32306 USA

[8] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Nashville, TN USA

关键词: Glucagon-like peptide 1 receptor;    liraglutide;    group 2 innate lymphoid cells;    IL-33;    Alternaria;   

DOI  :  10.1016/j.jaci.2017.11.043

来源: Elsevier

【 摘 要 】

Background: IL-33 is one of the most consistently associated gene candidates for asthma identified by using a genome-wide association study. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type 2 cytokine production from both group 2 innate lymphoid cells (ILC2s) and T(H)2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells. Objective: We sought to determine the effect of glucagon-like peptide 1 receptor (GLP-1R) signaling on aeroallergen-induced airway IL-33 production and release and on innate type 2 airway inflammation. Methods: BALB/c mice were challenged intranasally with Alternaria extract for 4 consecutive days. GLP-1Ragonist or vehicle was administered starting either 2 days before the first Alternaria extract challenge or 1 day after the first Alternaria extract challenge. Results: GLP-1R agonist treatment starting 2 days before the first Alternaria extract challenge decreased IL-33 release in the bronchoalveolar lavage fluid and dual oxidase 1 (Duox1) mRNA expression 1 hour after the first Alternaria extract challenge and IL-33 expression in lung epithelial cells 24 hours after the last Alternaria extract challenge. Furthermore, GLP-1R agonist significantly decreased the number of ILC2s expressing IL-5 and IL-13, lung protein expression of type 2 cytokines and chemokines, the number of perivascular eosinophils, mucus production, and airway responsiveness compared with vehicle treatment. GLP-1R agonist treatment starting 1 day after the first Alternaria extract challenge also significantly decreased eosinophilia and type 2 cytokine and chemokine expression in the airway after 4 days of Alternaria extract challenge. Conclusion: These results reveal that GLP-1R signaling might be a therapy to reduce IL-33 release and inhibit the ILC2 response to protease-containing aeroallergens, such as Alternaria.

【 授权许可】

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