TY - JOUR
T1 - Mucosal type 2 innate lymphoid cells are a key component of the allergic response to aeroallergens
AU - Dhariwal, Jaideep
AU - Cameron, Aoife
AU - Trujillo-Torralbo, Maria Belen
AU - Del Rosario, Ajerico
AU - Bakhsoliani, Eteri
AU - Paulsen, Malte
AU - Jackson, David J.
AU - Edwards, Michael R.
AU - Rana, Batika M.J.
AU - Cousins, David J.
AU - Hansel, Trevor T.
AU - Johnston, Sebastian L.
AU - Walton, Ross P.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - Rationale: Newly characterized type 2 innate lymphoid cells (ILC2s) display potent type 2 effector functionality; however, their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterize the airway mucosa is invasive, poorly tolerated, and does not allow for sequential sampling. Objectives: To assess the role of ILC2s during nasal allergen challenge in subjects with allergic rhinitis using novel noninvasive methodology. Methods: We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of ILC2s and granulocytes to the upper airways of subjects with atopy and healthy subjects after allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption. Measurements and Main Results: After an allergen challenge, subjects with atopy displayed rapid induction of upper airway symptoms, an enrichment of ILC2s, eosinophils, and neutrophils, along with increased production of IL-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared with healthy subjects. The most pronounced ILC2 recruitment was observed in subjects with elevated serum IgE and airway eosinophilia. Conclusions: The rapid recruitment of ILC2s to the upper airways of allergic patients with rhinitis, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergens in the airways. The novel methodology described herein enables the analysis of rare cell populations from noninvasive serial tissue sampling.
AB - Rationale: Newly characterized type 2 innate lymphoid cells (ILC2s) display potent type 2 effector functionality; however, their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterize the airway mucosa is invasive, poorly tolerated, and does not allow for sequential sampling. Objectives: To assess the role of ILC2s during nasal allergen challenge in subjects with allergic rhinitis using novel noninvasive methodology. Methods: We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of ILC2s and granulocytes to the upper airways of subjects with atopy and healthy subjects after allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption. Measurements and Main Results: After an allergen challenge, subjects with atopy displayed rapid induction of upper airway symptoms, an enrichment of ILC2s, eosinophils, and neutrophils, along with increased production of IL-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared with healthy subjects. The most pronounced ILC2 recruitment was observed in subjects with elevated serum IgE and airway eosinophilia. Conclusions: The rapid recruitment of ILC2s to the upper airways of allergic patients with rhinitis, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergens in the airways. The novel methodology described herein enables the analysis of rare cell populations from noninvasive serial tissue sampling.
KW - Allergic airway inflammation
KW - Asthma
KW - ILC2
KW - Th2
UR - http://www.scopus.com/inward/record.url?scp=85021049807&partnerID=8YFLogxK
U2 - 10.1164/rccm.201609-1846OC
DO - 10.1164/rccm.201609-1846OC
M3 - Article
C2 - 28085492
AN - SCOPUS:85021049807
SN - 1073-449X
VL - 195
SP - 1586
EP - 1596
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 12
ER -