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OBJECTIVES: Amish children raised on traditional farms have lower atopy and asthma risk than Hutterite children raised on modern farms. In our previous study, we established that the Amish environment affects the innate immune response to lower asthma and atopy risk. Herein we investigated the T cell phenotypes in the same Amish and Hutterite children as in our earlier study to elucidate how this altered innate immunity effects adaptive T cells. METHODS: Blood was collected from 30 Amish and 30 Hutterite age and sex-matched children; cells were cryopreserved until analysis. Flow cytometry was used to analyze cell subsets. Atopy was determined by allergen-specific and total IgE levels. RESULTS: Children exposed to Amish farms had increased activated Treg phenotypes, while conventional CD4 T cell expressed lower levels of co-stimulation molecules and other activation markers. The increase in circulating activated Tregs was associated with increase in inhibitory receptors on monocytes in Amish, but not Hutterite, children. Strikingly, the Amish children had a higher proportion of CD28null CD8 T cells than Hutterite children (non-parametric t test p

Soluble human leukocyte antigen-G (sHLA-G), an immunomodulatory molecule associated with suppression of inflammation, is elevated in the airways of asthmatic patients with a low inflammatory endotype as evidenced by low airway eosinophils and low exhaled nitric oxide.

Background We previously reported an interaction between maternal asthma and the child's HLA-G genotype on the child's subsequent risk for asthma. The implicated single nucleotide polymorphism at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs. Objective The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. Methods We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family ( miR-148a , miR-148b , and miR-152 ) transcript levels in airway epithelial cells from the same subjects. Results miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). Conclusion These combined results are consistent with +3142 allele–specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mother's children persist into adulthood.

Previously, we showed that an ongoing nasal allergic response augmented bacterial sinusitis in mice. In those experiments mice were sensitized to ovalbumin (OVA) by means of intraperitoneal injections of OVA-alum and then exposed to OVA intranasally before being infected with Streptococcus pneumoniae.We sought to study the importance of TH2 cells and to eliminate potential alum effects.In this study we sensitized mice by adoptively transferring OVA-specific TH2- or TH1-skewed cells.TH2 passive sensitization followed by intranasal OVA showed a robust local eosinophilic response (5-fold increase) compared with that seen in mice with only TH2 passive sensitization alone (P.001). Mice with TH2 passive sensitization and intranasal OVA exposure followed by infection showed an increase in the number of recovered S pneumoniae (P.05) and an increase in sinus inflammation compared with that seen in those with infection alone (P.01). In contrast, mice passively sensitized with TH1 followed by intranasal OVA exposure and infection showed no significant increase in the recovery of S pneumoniae and sinus inflammation compared with those with infection alone.These data support the importance of antigen-stimulated TH2 cells in the augmented response to infection in allergic mice. Whether the increased infection is related to the direct effect of TH2 cells and their cytokines or subsequent recruitment of other cells, such as eosinophils, will be determined in further studies.