Type 2 innate lymphoid cells expressing death receptor 3 are increased in airway of mild atopic asthmatic subject following allergen inhalation challenge
Monday, March 5, 2018: 2:45 PM
S220EF (Convention Center)
Kentaro Machida, MD, PhD, , , , , ,

Type 2 innate lymphoid cells (ILC2) are implicated in the initiation and propagation of eosinophilic asthma. To understand novel mechanisms of ILC2 activation, we investigated the role of death receptor 3 (DR3) and its cognate ligand, tumor necrosis factor like protein 1A (TL1A) in mediating ILC2 activation in allergic asthmatic responses.


Consenting mild atopic asthmatics (n=10) were recruited to a diluent-controlled allergen challenge crossover study. All subjects developed allergen induced dual bronchoconstriction, airway eosinophilia and increased methacholine airway responsiveness. By flow cytometry, induced sputum extracted ILC2 (lin-FcεRI-CD45+CD127+ST2+ CRTH2+) were identified and DR3 expression enumerated. In induced sputum supernatants, we used ELISA to assess TL1A levels. In functional studies, ILC2 from blood were stimulated with IL-2 and subsequent responses to TL1A were assessed, in vitro.


There was a significant increase in DR3+ILC2, 24 hours post-allergen challenge compared to pre-allergen and 24h post-diluent challenge (64±28 vs. 12±6 and 20±9 cells/ml; p<0.05 and p<0.01, respectively). Sputum supernatant levels of TL1A were significantly increased 24 h post allergen challenge compared to pre-allergen levels and 24h post-diluent challenge (3389±1904 vs. 983±796 and 908±832 pg/mL, p<0.05, respectively). Incubation with IL-2 significantly up-regulated DR3 expression on ILC2, and pre-incubation with IL-2 compared to diluent resulted in significantly increased IL-5+ILC2 in response to TL1A stimulation, in vitro.


Allergen challenge increases DR3 expression on ILC2 and levels of TL1A in the airway of atopic asthmatics. We propose that the TL1A/DR3 axis may contribute to allergen induced eosinophilic asthmatic inflammation through increased type 2 cytokine production by airway ILC2.