| First Author | Jang S | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 10 | Pages | 5835-44 |
| PubMed ID | 20944009 | Mgi Jnum | J:165624 |
| Mgi Id | MGI:4837941 | Doi | 10.4049/jimmunol.1000175 |
| Citation | Jang S, et al. (2010) Notch Ligand Delta-Like 4 Regulates Development and Pathogenesis of Allergic Airway Responses by Modulating IL-2 Production and Th2 Immunity. J Immunol 185(10):5835-44 |
| abstractText | Activation of the canonical Notch pathways has been implicated in Th cell differentiation, but the role of specific Notch ligands in Th2-mediated allergic airway responses has not been completely elucidated. In this study, we show that delta-like ligand 4 (Dll4) was upregulated on dendritic cells in response to cockroach allergen. Blocking Dll4 in vivo during either the primary or secondary response enhanced allergen-induced pathogenic consequences including airway hyperresponsiveness and mucus production via increased Th2 cytokines. In vitro assays demonstrated that Dll4 regulates IL-2 in T cells from established Th2 responses as well as during primary stimulation. Notably, Dll4 blockade during the primary, but not the secondary, response increased IL-2 levels in lung and lymph node of allergic mice. The in vivo neutralization of Dll4 was associated with increased expansion and decreased apoptosis during the primary allergen sensitization. Moreover, Dll4-mediated Notch activation of T cells during primary stimulation in vitro increased apoptosis during the contraction/resting phase of the response, which could be rescued by exogenous IL-2. Consistent with the role for Dll4-mediated IL-2 regulation in overall T cell function, the frequency of IL-4-producing cells was also significantly altered by Dll4 both in vivo and in vitro. These data demonstrate a regulatory role of Dll4 both in initial Th2 differentiation and in Th2 cytokine production in established allergic responses. |
