| First Author | Shrestha B | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 102 |
| Issue | 1 | Pages | 153-161 |
| PubMed ID | 28389622 | Mgi Jnum | J:278862 |
| Mgi Id | MGI:6359202 | Doi | 10.1189/jlb.4A1216-536R |
| Citation | Shrestha B, et al. (2017) IL-4Ralpha on dendritic cells in neonates and Th2 immunopathology in respiratory syncytial virus infection. J Leukoc Biol 102(1):153-161 |
| abstractText | Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children, and severe RSV infection early in life has been associated with asthma development. Using a neonatal mouse model, we have shown that down-regulation of IL-4 receptor alpha (IL-4Ralpha) with antisense oligonucleotides in the lung during neonatal infection protected from RSV immunopathophysiology. Significant down-regulation of IL-4Ralpha was observed on pulmonary CD11b(+) myeloid dendritic cells (mDCs) suggesting a role for IL-4Ralpha on mDCs in the immunopathogenesis of neonatal RSV infection. Here, we demonstrated that neonatal CD11b(+) mDCs expressed higher levels of IL-4Ralpha than their adult counterparts. Because CD11b(+) mDCs mainly present antigens to CD4(+) T cells, we hypothesized that increased expression of IL-4Ralpha on neonatal CD11b(+) mDCs was responsible for Th2 - biased RSV immunopathophysiology. Indeed, when IL-4Ralpha was selectively deleted from CD11b(+) mDCs, the immunopathophysiology typically observed following RSV reinfection was ablated, including Th2 inflammation, airway-mucus hyperproduction, and pulmonary dysfunction. Further, overexpression of IL-4Ralpha on adult CD11b(+) DCs and their adoptive transfer into adult mice was able to recapitulate the Th2-biased RSV immunopathology typically observed only in neonates infected with RSV. IL-4Ralpha levels on CD11c(+) cells were inversely correlated with maturation status of CD11b(+) mDCs upon RSV infection. Our data demonstrate that developmentally regulated IL-4Ralpha expression is critical for the maturity of pulmonary CD11b(+) mDCs and the Th2-biased immunopathogenesis of neonatal RSV infection. |
