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Severe Asthma Research - February 2016

Christina E Ciaccio, MD, MSc

Christina E Ciaccio, MD, MSc
Assistant Professor of Pediatrics
University of Chicago Medicine
Comer Children’s Hospital
Chicago, Illinois, United States

Toll-like Receptor 7 Is Reduced in Severe Asthma and Linked to Altered MicroRNA Profile

In this study, investigators sought to determine if reduced TLR 7 signaling was the cause of reduced interferon response to rhinovirus infection, an infection thought to be responsible for as much as 50% of asthma exacerbations in adult asthmatics.  Alveolar macrophages were recovered via bronchoscopy from adults with asthma (n=43; severe asthma n=35) as well as healthy controls (n=44).  Compared to the controls, those with severe asthma who participated in the study were older and had a higher BMI on average.  Twenty-four hours after stimulation with rhinovirus, alveolar macrophages from severe asthmatics produced lower amounts of IFNα and IFNβ compared to controls.  In addition, TLR7 expression on alveolar macrophages was reduced in those with severe asthma.  No other differences in pattern recognition receptors between those with severe asthma and controls were seen.  The alveolar macrophages were then treated with a direct TLR7 agonist and again, those from subjects with severe asthma had reduced production of IFNα and IFNβ.  Finally, the investigators identified 3 miRNAs which were increased in those with severe asthma and potentially interacted with TLR7, and knockdown of these miRNAs restored TLR7 function.  These preliminary findings provide the basis for potential new therapeutic options for severe asthma.

Rupani H, Martinez-Nunez RT, Dennison P, Lau LC, Jayasekera N et al. Toll-like receptor 7 is reduced in severe asthma and linked to altered microRNA profile. American Journal of Respiratory and Critical Care Medicine 2016; published online ahead of print, January 27. (doi:10.1164/rccm.201502-0280OC)