Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age

Abstract

Objective. Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10-fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy. Methods. Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t-distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep. Results. Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty-four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptorhomologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age." Conclusion. Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life.

Crosstalk between ILC2s and Th2 CD4+ T Cells in Lung Disease

“…In humans, ILC2s accumulate in fetal lungs at 10-fold higher levels than adult lungs [ 53 ]. Another study also detected ILC2s in fetal and adult lungs, which accounted for more of the total ILC in adult lungs [ 54 ].…”

“…In other words, the existence of ILC2s in human lungs is based on suggestions rather than conclusive evidence. Better understanding of human lung ILC2s may come from less evasive samples such as human umbilical cord blood [ 53 ]/peripheral blood, or sputum and BALF [ 56 – 58 ], or humanized mice models [ 59 ]. Therefore, further study on human lung ILC2s, preferably directly, is needed for a better understanding of their characteristics and functions.…”

From preschool wheezing to asthma: Immunological determinants

“…32 Another study showed an interaction between ECs and ILC2s that play a major role in maintaining chronic asthma. 33 Moreover, a cord blood ILC2 subpopulation was associated with lower infant lung function, 34 and recent studies showed that increased ILC2 numbers were associated with RSV-induced bronchiolitis and recurrent wheezing, 35 potentially involved in increased susceptibility to asthma. However, as ILCs are a quite newly studied immune cell population, not many data report on the impact of ILC2s during wheeze and progression to asthma.…”