TY - JOUR T1 - LSC 2013 abstract - Microbial colonization instigates a lung-specific immunoregulatory pathway that protects against exaggerated allergic inflammation JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - PP163 AU - Eva Gollwitzer AU - Benjamin Marsland Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/PP163.abstract N2 - A growing body of evidence indicates that events early in childhood can predispose individuals to chronic lung diseases. We hypothesized that exposure to environmental allergens or pathogens during immunologically distinct developmental windows might underlie this phenomenon. To first gain insight into the pulmonary immune maturation process, we characterized the nature of immune cells in the murine lung from birth until adulthood. In contrast to B and T cells, dendritic cell (DC) populations exhibited a lung-specific maturation profile, reflected by differences in frequency and phenotype. Of particular note was the expression kinetics of Programmed cell death 1 ligand 1 (PD-L1) on the surface of CD11b+ conventional DCs, which exhibited a peak in expression one week after birth, before returning to levels found in adults. The elevated frequency of PD-L1-expressing DCs in the lungs of neonatal mice was linked with the induction of inducible T regulatory cells (iTregs), highlighting a key developmental step for tolerance to exogenous antigens. In order to determine whether this was due to an intrinsic maturation programme or driven by environmental factors, we analysed cell maturation in axenic mice. We found that microbial exposure was the key instigating stimuli for this DC-PD-L1-iTreg tolerance pathway. Subsequent in vivo depletion studies showed that this pathway was a non-redundant mechanism for protecting the lung against exaggerated inflammation towards environmental allergens. Overall our data shows that there is a dynamic lung-specific immunoregulatory process during the perinatal period, which is driven by the airway microbiome. ER -