Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma

Publication date: December 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 6

Author(s): Matthew C. Altman, Elizabeth Whalen, Alkis Togias, George T. O'Connor, Leonard B. Bacharier, Gordon R. Bloomberg, Meyer Kattan, Robert A. Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M. Visness, William W. Busse, James E. Gern

Background

Childhood asthma in inner-city populations is a major public health burden, and understanding early-life immune mechanisms that promote asthma onset is key to disease prevention. Children with asthma demonstrate a high prevalence of aeroallergen sensitization and T_H2-type inflammation; however, the early-life immune events that lead to T_H2 skewing and disease development are unknown.

Objective

We sought to use RNA sequencing of PBMCs collected at age 2 years to determine networks of immune responses that occur in children with allergy and asthma.

Methods

In an inner-city birth cohort with high asthma risk, we compared gene expression using RNA sequencing in PBMCs collected at age 2 years between children with 2 or more aeroallergen sensitizations, including dust mite, cockroach, or both, by age 3 years and asthma by age 7 years (cases) and matched control subjects who did not have any aeroallergen sensitization or asthma by age 7 years.

Results

PBMCs from the cases showed higher levels of expression of natural killer (NK) cell–related genes. After cockroach or dust mite allergen but not tetanus antigen stimulation, PBMCs from the cases compared with the control subjects showed differential expression of 244 genes. This gene set included upregulation of a densely interconnected NK cell–like gene network reflecting a pattern of cell activation and induction of inflammatory signaling molecules, including the key T_H2-type cytokines IL9, IL13, and CCL17, as well as a dendritic cell–like gene network, including upregulation of CD1 lipid antigen presentation molecules. The NK cell–like response was reproducible in an independent group of children with later-onset allergic sensitization and asthma and was found to be specific to only those children with both aeroallergen sensitization and asthma.

Conclusion

These findings provide important mechanistic insight into an early-life immune pathway involved in T_H2 polarization, leading to the development of allergic asthma.

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