Article Text

PDF

Novel mechanisms driving airway inflammation in asthma
S35 Rapamycin inhibits IL-33-induced, nuocyte-driven airway inflammation
  1. A S Mirchandani,
  2. R J Salmond,
  3. C J Bain,
  4. F Y Liew
  1. University of Glasgow, Glasgow, UK

Abstract

Introduction IL-33 is an innate cytokine that promotes Th2 responses in both the innate and the adaptive immune systems, with an established role in allergic airway inflammation.1 The signalling pathway of IL-33/ ST2 is incompletely understood and the cells driving IL-33-mediated inflammation have remained elusive. Nuocytes, also known as natural helper cells, are a novel subpopulation of lineage negative innate cells that respond to IL-33 and IL-2.2 Rapamycin is a macrolide antibiotic that allosterically blocks mTOR, a serine-threonine kinase involved in numerous cellular signalling pathways.

Aim To determine the role of mTOR in IL-33-induced airway inflammation and the effect of rapamycin on IL-33-induced nuocytes in the lung.

Method BALB/c mice were treated with 1 μg of IL-33 intranasally for 5 consecutive days in the presence or absence of rapamycin. Bronchoalveolar lavage (BAL) for cellular and cytokine analysis was performed. Fluorescence-activated cell sorting (FACS) of lung digests were analysed for intracellular IL-5 and cell surface markers.

Results IL-33 induced profound airway cellular infiltration noted in the BAL that was significantly inhibited by rapamycin. Cytokine levels from BAL fluid were also significantly reduced in mice treated with IL-33+ rapamycin. FACS analysis of lung digests demonstrated that IL-33 induced the expansion of lineage negative cells, in keeping with a population of nuocytes, which were the main source of IL-5 in the lung. Furthermore, this population of cells was suppressed by rapamycin.

Discussion Intranasal IL-33 drives mTOR-dependant airway inflammation. Nuocytes are the main source of IL-5 in IL-33-driven airway inflammation. Rapamycin inhibits the production of IL-5 and IL-13 in vivo as well as the expansion of nuocytes in the lung.

Abstract S35 Figure 1

BALB/c mice were treated intranasally with 1 μg IL-33 in the presence or absence of 1 mg/kg rapamycin for 5 consecutive days. The mice were sacrificed on day 6 and BAL total cell counts were performed. ***=p<0.001.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.