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The intersect of genetics, environment, and microbiota in asthma-perspectives and challengesIn asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. This review covers recent developments in our understanding of this interaction: the "microbial hypothesis" and the "farm effect"; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures.
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Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studiesResults from recent clinical studies suggest potential efficacy of immune training (IT)-based approaches for protection against severe lower respiratory tract infections in infants, but underlying mechanisms are unclear.
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Asthma and allergies in a cohort of adolescents conceived with ARTResearch question: Are asthma and allergies more common in adolescents conceived with assisted reproductive technologies (ART) compared with adolescents conceived without?
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Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networksThe immunological changes underpinning acquisition of remission (also called sustained unresponsiveness) following food immunotherapy remain poorly defined. Limited access to effective therapies and biosamples from treatment responders has prevented progress. Probiotic peanut oral immunotherapy is highly effective at inducing remission, providing an opportunity to investigate immune changes.
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Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.
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Vitamin D over the first decade and susceptibility to childhood allergy and asthmaWe aimed to research relationships between 25(OH)D levels from birth to 10 y/o and susceptibility to allergic sensitization, respiratory issues and asthma.
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Early immunological influences on asthma development: opportunities for early interventionEarly immunological influences on asthma development: opportunities for early intervention
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Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infectionPoor maternal diet during pregnancy is a risk factor for severe lower respiratory infections in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell recruitment and perturbation of regulatory T cell expansion in the lungs.
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Innate Immune Training for Prevention of Recurrent Wheeze in Early ChildhoodPat Deborah Holt Strickland PhD, DSc, FRCPath, FRCPI, FAA PhD Emeritus Honorary Researcher Head, Pregnancy and Early Life Immunology Patrick.Holt@
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Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor ProgrammingWe recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis.