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

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 receptor-homologous 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.