It is known that fine particles in the air including particle pollutants participate in allergic inflammation. However, the molecular mechanisms by which fine particles induce and exacerbate allergic responses are unknown. Previously, we have demonstrated that fine particles such as alum and silica induce cell death and release IL-1α in alveolar macrophages. Dead cell-derived IL-1α is involved in IgE production. Interestingly, we also found that IL-1α promotes inducible bronchus-associated lymphoid tissue (iBALT) formation in the lungs, suggesting that iBALT formation plays an important role for IgE responses through IL-1α release by alveolar macrophages death. In this study, we further examined the mechanisms of iBALT formations and IgE responses induced by fine particles.
Alum and silica were used as potent allergic inducers. These fine particles were administered by intratracheal (i.t.) instillation and then mice were exposed to OVA aerosol. Previously, we found that fine particle induce iBALT formation and IgE responses; those were regulated by IL-1R signaling. We also observed that DC migration into the lungs attenuated in IL-1R1 KO mice. Furthermore, using CD11c-DTR mice, we observed that levels of IgE responses and iBALT formation were reduced by the depletion of CD11c+ cells. In addition to DCs, we also found the critical role of Tfh cells in iBALT formation. Using Cd4-cre Bcl6flox/floxmice, as a model of Tfh-deficient mouse, we observed that Tfh-deficiency showed reduced levels of IgE responses and iBALT formation, the same way as DC depletion experiment.
These results indicate that Tfh cells, DCs and iBALT formation play a critical role for inhaled fine particle-induced IgE production and allergic inflammation in the lungs