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 contribution
posted 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. WaltonRationale: 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.
Funding
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.
History
Citation
American Journal of Respiratory and Critical Care Medicine, 2017Author affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and InflammationVersion
- AM (Accepted Manuscript)