CD301b Dendritic Cell-derived IL-2 Dictates CD4 T Helper Cell Differentiation

Overview

Journal Nat Commun

Specialty Biology

Date 2025 Feb 26

PMID 40011469

Authors

Naoya Tatsumi

Jihad El-Fenej

Alejandro Davila-Pagan

Yosuke Kumamoto

Affiliations

Soon will be listed here.

Abstract

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.

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