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

Author

Listed:
  • Naoya Tatsumi

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Jihad El-Fenej

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Alejandro Davila-Pagan

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Yosuke Kumamoto

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

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.

Suggested Citation

  • Naoya Tatsumi & Jihad El-Fenej & Alejandro Davila-Pagan & Yosuke Kumamoto, 2025. "CD301b+ dendritic cell-derived IL-2 dictates CD4+ T helper cell differentiation," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55916-9
    DOI: 10.1038/s41467-025-55916-9
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