First Author | Zhang Y | Year | 2012 |
Journal | Eur J Immunol | Volume | 42 |
Issue | 7 | Pages | 1735-43 |
PubMed ID | 22585305 | Mgi Jnum | J:187770 |
Mgi Id | MGI:5438172 | Doi | 10.1002/eji.201142123 |
Citation | Zhang Y, et al. (2012) DC-derived TSLP promotes Th2 polarization in LPS-primed allergic airway inflammation. Eur J Immunol 42(7):1735-43 |
abstractText | Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of allergic diseases. Whether and how TSLP is involved in the initial priming of T helper type-2 (Th2) differentiation against harmless antigen remains unclear. Using an intranasal sensitization protocol with OVA and LPS, we showed that TSLP signaling is required for low-dose LPS-induced Th2 inflammation, but not for high-dose LPS-induced Th1 immunity. We further demonstrated that low-dose LPS-activated bone marrow-derived dendritic cells expressed relatively high Tslp but low Il12a, and were able to prime naive DO11.10 T cells to differentiate into Th2 cells in a TSLP-dependent manner. After transfer into wild-type recipient mice, the low-dose LPS-activated OVA-loaded dendritic cells (DCs) induced airway eosinophilia, but primed neutrophil-dominated airway inflammation when TSLP-deficient DCs were used. These studies demonstrate that TSLP released by DCs in response to a low concentration of LPS plays a role in priming Th2 differentiation and thus may serve as a polarizing third signal, in addition to antigen/MHC class II and co-stimulatory factors, from antigen-presenting DCs to direct effector T-cell differentiation. |