Instruction of Th2 cell fate by CD301b⁺ DC-derived IL-2

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B610
Abstract ID: 4605

Presenting Author:
Naoya Tatsumi , Visiting researcher at Rutgers New Jersey Med. Sch.

Abstract:

The differentiation of effector T helper (Th) cells is a pivotal process in shaping adaptive immunity. Many studies have suggested that different dendritic cell (DC) subsets induce different types of Th cells. However, the mechanism behind Th type 2 (Th2) cell fate instruction has remained most elusive, largely due to the unidentified primary cue from DCs. We and others previously have shown that CD301b⁺ DCs, a major subset of migratory cDC2s, are specifically required for the Th2 differentiation of antigen-specific CD4 T cells induced by allergens, adjuvants, or by helminth infection. Here we demonstrate that CD301b⁺ DCs instruct the Th2 cell fate through cognate interaction by triggering IL-2 receptor signaling in antigen specific CD4 T cells. Mechanistically, upon cognate interaction, CD40 engagement enhances selective IL-2 production from CD301b⁺ DCs to maximize CD25 expression in antigen-specific CD4 T cells. The maximal CD25 upregulation in antigen-specific CD4 T cells is specifically required for their differentiation into Th2 cells. Furthermore, the activation of STAT5, a major downstream of IL-2-CD25 signaling, in antigen-specific CD4 T cells requires CD25 expression in CD301b⁺ DCs, suggesting that CD301b⁺ DC-intrinsic CD25 facilitates the directed action of IL-2 toward cognate CD4 T cells. These findings reveal the critical role of DC-intrinsic CD40-IL-2 axis in dictating Th2 cell fate.