Final Mucosal type 2 innate lymphoid cells identified as central to the allergic response in asthma.pdf (1.85 MB)
Mucosal type 2 innate lymphoid cells are a key component of the allergic response to aeroallergen
journal contributionposted on 2017-01-09, 13:09 authored by J. Dhariwal, A. Cameron, M. Trujillo-Torralbo, A. del Rosario, E. Bakhsoliani, M. Paulsen, D. J. Jackson, M. R. Edwards, B. M. J. Rana, David J. Cousins, T. T. Hansel, S. L. Johnston, R. P. Walton
Rationale: Newly characterised type 2 innate lymphoid cells display potent type 2 effector functionality, however their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterise the airway mucosa is invasive, poorly tolerated and does not allow for sequential sampling. Objectives: To assess the role of type 2 innate lymphoid cells during nasal allergen challenge in subjects with allergic rhinitis, using novel non-invasive methodology. Methods: We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of type 2 innate lymphoid cells and granulocytes to the upper airways of atopic and healthy subjects following allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption. Measurements and Main Results: Following allergen challenge, atopic subjects displayed rapid induction of upper airway symptoms, an enrichment of type 2 innate lymphoid cells, eosinophils and neutrophils, along with increased production of interleukin-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared to healthy subjects. The most pronounced type 2 innate lymphoid cell recruitment was observed in patients with elevated serum IgE and airway eosinophilia. Conclusions: The rapid recruitment of type 2 innate lymphoid cells to the upper airways of allergic rhinitis patients, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergen in the airways. The novel methodology described herein enables the analysis of rare cell populations from non-invasive, serial tissue sampling.
This work was supported by a Medical Research Council (MRC) and GlaxoSmithKline Strategic Alliance Programme Grant number G1100238, the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme and the MRC and Asthma UK Centre Grant G1000758. DJC also acknowledges financial support from NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London and from the NIHR Leicester Respiratory Biomedical Research Unit. SLJ is the Asthma UK Clinical Chair (grant CH11SJ) and is an NIHR Senior Investigator.
CitationAmerican Journal of Respiratory and Critical Care Medicine, 2017
Author affiliation/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation
- AM (Accepted Manuscript)