Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity

Over the past 25 years, the rates of both obesity and asthma have increased dramatically.  These are related to one another, with a 92% increased risk of asthma in people whose body mass index (BMI) exceeds 30 kg/m². People who do lose weight through bariatric surgery or dietary restriction, tend to show improvement in their bronchial hyperresponsiveness, the major feature of asthma.  The reason for this correlation is not well understood.  IL-33, a intercellular messenger that skews helper T cells towards allergies, is produced by fat cells.  IL33 also induces type 2 and type 3 innate lymphoid cells (ILC2 and ILC3), two more recently identified sets of immune cells in fat and the lungs. 

In this month’s issue of the Journal of Allergy and Clinical Immunology, Everaere and colleagues use mouse models to investigate the roles of innate lymphoid cells in the correlation between asthma and obesity (J Allergy Clin Immunol 2016; 138(5): 1309-1318).  The mice were given a high-fat diet to induce obesity and were then sensitized to dust mites.  Their lung secretions were isolated by bronchoaveolar lavage (BAL) and checked for various proteins, RNA, and cell types by histology and flow cytometry. 

They found that nonsensitized obese mice had increased ILC counts and tissue eosinophils, cells that mediate damage in asthma, compared to lean mice.  These mice also had high IL33 and IL-1-Beta levels.  When ILCs were depleted using an anti-CD90 antibody, there was decreased infiltration by cells that prompt allergic inflammation, such as TH2 and TH17 cells.

Altogether, these results suggest that ILC2s and ILC3s mediate and exacerbate airway inflammation in obese mice.  This opens the possibility of using anti-IL5 antibodies in treating asthma for obese patients.