| First Author | Dittrich AM | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 10 | Pages | 7307-15 |
| PubMed ID | 18981153 | Mgi Jnum | J:275199 |
| Mgi Id | MGI:6304201 | Doi | 10.4049/jimmunol.181.10.7307 |
| Citation | Dittrich AM, et al. (2008) A new mechanism for inhalational priming: IL-4 bypasses innate immune signals. J Immunol 181(10):7307-15 |
| abstractText | Signaling via innate immune mechanisms is considered pivotal for T cell-mediated responses to inhaled Ags. Furthermore, Th2 cells specific for one inhaled Ag can facilitate priming of naive T cells to unrelated new inhaled Ags, a process we call "Th2 collateral priming". Interestingly, our previous studies showed that collateral priming is independent of signals via the innate immune system but depends on IL-4 secretion by CD4(+) T cells. We thus hypothesized that IL-4 can bypass the need for signals via the innate immune system, considered essential for pulmonary priming. Indeed, we were able to show that IL-4 bypasses the requirement for TLR4- and MyD88-mediated signaling for responses to new allergens. Furthermore, we characterized the mechanisms by which IL-4 primes for new inhaled allergens: "IL-4-dependent pulmonary priming" relies on IL-4 receptor expression on hematopoietic cells and structural cells. Transfer experiments indicate that within the hematopoietic compartment both T cells and dendritic cells need to express the IL-4 receptor. Finally, we were able to show that IL-4 induces recruitment and maturation of myeloid dendritic cells in vivo and increases T cell recruitment to the draining lymph nodes. Our findings bring new mechanistic knowledge to the phenomenon of polysensitization and primary sensitization in asthma. |
