Pathogenic Mechanisms of Allergic Inflammation : Atopic Asthma as a Paradigm

摘要: Prospective studies tracking birth cohorts over periods of years indicate that the seeds for atopic asthma in adulthood are sewn during early life. The key events involve programming functional phenotypes within immune and respiratory systems which determine long-term responsiveness to ubiquitous environmental stimuli, particularly viruses aeroallergens. A crucial component pathogenesis is sensitization aeroallergens stemming from a failure mucosal tolerance mechanisms preschool years, associated with delayed postnatal maturation range adaptive innate functions. These maturational defects also increase risk severe infections, combination infections maximizes development persistent phenotype. Interactions between immunoinflammatory pathways stimulated by these agents sustain disease later life as major triggers exacerbations. Recent on nature interactions suggest operation an infection-associated lung:bone marrow axis involving upregulation FcERlalpha myeloid precursor populations prior their migration airways, thus amplifying local inflammation via IgE-mediated recruitment bystander effector mechanisms. participants process airway dendritic cells adjacent epithelial cells, transiting CD4(+) regulatory T-cell populations, increasingly detailed characterization roles at different stages opening up novel possibilities therapeutic control asthma. Of particular interest application genomics-based approaches drug target identification cell interest, exemplified recent findings discussed below relating gene network(s) triggered activation Th2-memory atopics.