Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity

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• 作者：Laetitia Everaere ; PhD^a ; ^b ; ^c ; ^d ; ^e ; ^f ; Saliha Ait-Yahia ; PhD^a ; ^b ; ^c ; ^d ; Olivier Molendi-Coste ; PhD^c ; ^d ; ^e ; ^f ; Han Vorng ; BSc^a ; ^b ; ^c ; ^d ; Sandrine Quemener ; MSc^c ; ^d ; ^e ; ^f ; Pauline LeVu ; MSc^c ; ^d ; ^e ; ^f ; Sebastien Fleury ; BSc^c ; ^d ; ^e ; ^f ; Emmanuel Bouchaert ; BSc^c ; ^d ; ^e ; ^f ; Ying Fan ; PhD^a ; ^b ; ^c ; ^d ; Catherine Duez ; PhD^a ; ^b ; ^c ; ^d ; Patricia de Nadai ; PhD^a ; ^b ; ^c ; ^d ; Bart Staels ; DPhSc^c ; ^d ; ^e ; ^f ; David Dombrowicz ; PhD^c ; ^d ; ^e ; ^f ; ^&lowast ; ; ^{david.dombrowicz@pasteur-lille.fr" class="auth_mail" title="E-mail the corresponding author} ; Anne Tsicopoulos ; MD^a ; ^b ; ^c ; ^d ; ^g ; ^&lowast ; ; ^{anne.tsicopoulos@pasteur-lille.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Innate lymphoid cells ; TH2 ; TH17 ; allergy ; asthma ; house dust mite ; obesity ; high-fat diet
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：138
• 期：5
• 页码：1309-1318.e11
• 全文大小：6388 K

文摘

Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR).

Objective

We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)–induced obesity.

Methods

Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs.

Results

HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T_H2 and T_H17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T_H2 and T_H17 infiltration.

Conclusion

These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s.