<p>T helper (Th) cell differentiation is fundamental to functional adaptive immunity. Different subsets of dendritic cells (DC) preferentially induce different types of Th cells, but the DC-derived mechanism for Th type 2 (Th2) differentiation is not fully understood. Here, we show that in mice, CD301b<sup>+</sup> DCs, a major Th2-inducing DC subset, drive Th2 differentiation through cognate interaction by rapidly inducing IL-2 receptor signalling in CD4<sup>+</sup> T cells. Mechanistically, CD40 engagement prompts IL-2 production selectively from CD301b<sup>+</sup> DCs to maximize CD25 expression in CD4<sup>+</sup> T cells, which instructs the Th2 fate decision, while simultaneously skewing CD4<sup>+</sup> T cells away from the T follicular helper fate. Moreover, CD301b<sup>+</sup> DCs utilize their own CD25 to facilitate directed action of IL-2 toward cognate CD4<sup>+</sup> T cells, as genetic deletion of CD25 in CD301b<sup>+</sup> DCs results in reduced IL-2-mediated signalling in antigen-specific CD4<sup>+</sup> T cells and hence their Th2 differentiation. These results highlight the critical role of DC-intrinsic CD40–IL-2 axis in Th cell fate decision.</p>

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CD301b+ dendritic cell-derived IL-2 dictates CD4+ T helper cell differentiation

  • Naoya Tatsumi,
  • Jihad El-Fenej,
  • Alejandro Davila-Pagan,
  • Yosuke Kumamoto

摘要

T helper (Th) cell differentiation is fundamental to functional adaptive immunity. Different subsets of dendritic cells (DC) preferentially induce different types of Th cells, but the DC-derived mechanism for Th type 2 (Th2) differentiation is not fully understood. Here, we show that in mice, CD301b+ DCs, a major Th2-inducing DC subset, drive Th2 differentiation through cognate interaction by rapidly inducing IL-2 receptor signalling in CD4+ T cells. Mechanistically, CD40 engagement prompts IL-2 production selectively from CD301b+ DCs to maximize CD25 expression in CD4+ T cells, which instructs the Th2 fate decision, while simultaneously skewing CD4+ T cells away from the T follicular helper fate. Moreover, CD301b+ DCs utilize their own CD25 to facilitate directed action of IL-2 toward cognate CD4+ T cells, as genetic deletion of CD25 in CD301b+ DCs results in reduced IL-2-mediated signalling in antigen-specific CD4+ T cells and hence their Th2 differentiation. These results highlight the critical role of DC-intrinsic CD40–IL-2 axis in Th cell fate decision.