Comparison of blood ILC2 cell numbers, phenotypes and proliferation between atopic severe asthma participants, healthy controls with atopy and non-atopic healthy controls

Abstract

Background: Group 2 innate lymphoid cells (ILC2s) are thought to play an important role in asthma by promoting type 2 inflammation.

Aims: To compare blood ILC2 cells between severe atopic, eosinophilic asthma (SA), atopic controls without asthma (AC) and healthy controls (HC).

Methods: HC and AC participants had normal lung function and no history of asthma. SA participants had GINA step 5 severe eosinophilic, allergic asthma. Peripheral blood mononuclear cells (PBMCs) were obtained from HC n=8, AC n=6 and SA n=10. ILCs were identified and sorted by flow cytometry, then cultured for 14 days with IL-2, IL-33, IL-25 and TSLP. We analysed ILC2 numbers and surface receptors for activation during sorting. ILC2 proliferative capacity was assessed on day 14 by flow cytometry.

Results: Subjects with SA were all treated with high dose of inhaled corticosteroids (ICS) (mean ± SD) 256.3 ± 62.32 (mcg/d). We found increased numbers of ILC2s/ml of blood (median (Q1, Q3)) of SA: 101 (61, 348), AC: 151 (99, 262) compared to HC: 60 (32, 107) (p<0.04). ILC1/ml of blood were also increased (median (Q1, Q3)) in SA: 345 (90, 401), AC: 190 (116, 342) compared to HC: 76 (31, 117) (p<0.02). Moreover, we found increased ILC2s per cell proliferative capacity (median (Q1, Q3)) of SA: 318 (39, 364), AC: 35 (12, 365) compared to HC: 5 (1, 69) (p<0.03).

Method: SA and AC group had higher number of ILC1 and ILC2 cells. In both groups, ILC2 cells exhibited increased proliferative capacity compared to ILC2s from HC group and this maybe greater in SA compared to AC. ILC2 cells were elevated in SA despite the use of high dose of ICS.