Allergen induced activation of NK cells represents an early life immune response in development of allergic asthma

Publication date: Available online 5 March 2018
Source:Journal of Allergy and Clinical Immunology
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
BackgroundChildhood 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 who develop asthma demonstrate a high prevalence of aeroallergen sensitization and T helper 2 (Th2)-type inflammation, however the early life immune events that lead to Th2 skewing and disease development are unknown.ObjectiveWe sought to use RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected at age 2 to determine networks of immune responses that occur in children who develop allergy and asthma.MethodsIn a high asthma risk inner city birth cohort, we compared gene expression by RNA sequencing in PBMCs collected at age 2 between children who developed ≥2 aeroallergen sensitizations including dust mite (DM) and/or cockroach (CR) by age 3 and asthma by age 7 (cases) and matched controls who did not develop any aeroallergen sensitization or asthma by age 7.ResultsPBMCs from the cases showed higher levels of expression of natural killer (NK) cell related genes. After CR or DM allergen but not tetanus antigen stimulation, PBMCs from the cases compared to the control group, 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 key Th2-type cytokines IL9, IL13, and CCL17 as well as a dendritic cell (DC)-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 that develop both aeroallergen sensitization and asthma.ConclusionThese findings provide important mechanistic insight into an early life immune pathway involved in Th2 polarization leading to development of allergic asthma.

Teaser

Inner city children who have cockroach and/or dust mite allergy as well as asthma at age 7 show exaggerated cytotoxic lymphocyte and lipid antigen presentation gene expression responses to allergen stimulation of PBMCs collected at age 2.


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