Dendritic cells elicit allergic immune responses in a CCR7-dependent fashion (103.10)

Abstract

Abstract DCs are key in mounting allergic immunity by mobilizing from allergen exposed sites to lymphoid tissues for T cell activation. However, whether the CCR7-CCL19/21 axis promotes DC mobilization and Th2 responses in allergy is incompletely understood. We thus sought to determine if CCR7 expression by DCs promotes allergy. Allergic conjunctivitis (AC) was evaluated in wild-type (WT) mice immunized via adoptive transfer with OVA/Alum-primed (WT) T cells. Mice were injected subconjunctivally (SCJ) with exogenous WT or CCR7 KO DCs (or PBS), and immediately instilled with OVA-loaded eye drops to induce AC. Clinical signs were scored biomicroscopically, and sera were sampled for OVA-specific IgE analysis. T cells were isolated for cytokine analyses to in vitro recall stimulation. Lastly, leukocytosis of collagenase-digested conjunctival cells was FACS analyzed. Upregulated CCR7 expression was confirmed of SCJ injected WT DCs found in lymph nodes of immunized mice following instillation of PE-OVA eye drops. Mice with WT DCs showed significant augmentation of clinical signs relative to sham controls. This was corroborated by a 2-fold increase in mast cell and eosinophil infiltration, 4-fold increase in IL-13 and IL-4, and an 8-fold increase in IgE (p<0.05). Strikingly, this augmentation was completely reversed in hosts with CCR7 KO DCs, and this abrogation was consistently seen in all parameters. Thus, our study suggests that DCs promote allergic immunity in a CCR7-dependent fashion.