Mucosal Associated Invariant T (MAIT) cells in lean and obese asthma

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B856
Abstract ID: 5016

Presenting Author:
Angela Cannata , PhD candidate at Cincinnati Children’s Hosp. Med. Ctr., Univ. of Cincinnati Col. of Med.

Abstract:

While lean asthma is associated with Th2-biased inflammation, obese asthmatics often exhibit limited Th2 markers and worsened diseased, suggesting that obese-asthma specific mechanisms are different and alternative therapeutics may be required. However, as obese asthma is primarily observed in women and inducing severe obesity (with metabolic dysfunction) in female mice (but not males) is difficult, mechanistic insights into obese asthma are limited. Here, we utilize a unique model wherein animals are fed a high fat diet (HFD) while housed at a higher ambient temperature. This approach is capable of inducing severe weight gain and metabolic dysfunction in both male and female mice. Using this model, we show that obese asthmatic females (but not males) demonstrate worse lung function and inflammation compared to lean females. Asthma in obese females was characterized by decreased Th2-associated inflammation and increased IL-17A production, a phenotype that closely models human disease. Increased IL-17A production was found primarily in pulmonary MAIT cells of obese asthmatic female mice suggesting an important role for these cells in disease. Supporting this, blocking MAIT cell activation in obese asthmatic females reduced disease outcomes to levels observed in lean asthmatic mice. These data suggest MAIT cells are uniquely pathogenic in obese asthmatic females and suggest a novel therapeutic intervention to improve asthma outcomes in a well-recognized, at-risk population.