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GM-CSF and specific type 2 cytokines induce CD103+ and CD301b+ cell states in cDC1s and cDC2s

Lukas Amon1, Damir Vurnek2, Anna Seichter3

  • 1Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91052 Erlangen, Germany; Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, 9052 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, 9000 Ghent, Belgium.

Cell Reports
|November 27, 2025
PubMed

Insights

Granulocyte/macrophage colony-stimulating factor (GM-CSF) drives the differentiation of conventional dendritic cells type 1 (cDC1s) and type 2 (cDC2s). CD301b+ cDC2s represent a cytokine-induced state, distinct from GM-CSF-driven cDC1s.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Conventional dendritic cells type 1 (cDC1s) and type 2 (cDC2s) exhibit significant heterogeneity.
  • The precise origin and identity of CD301b+ cDC2s, a subset of cDC2s, remain unclear.

Purpose of the Study:

  • To elucidate the developmental pathways and regulatory mechanisms governing CD301b+ cDC2s and CD103+ cDC1s.
  • To investigate the roles of granulocyte/macrophage colony-stimulating factor (GM-CSF) and type 2 cytokines in cDC differentiation.

Main Methods:

  • Analysis of dendritic cell progenitor differentiation in response to GM-CSF.
  • Assessment of CD103 and CD301b expression in vitro and in vivo.
  • Evaluation of T cell priming capacities and cytokine profiles of differentiated DCs.

Main Results:

  • CD301b+ cDC2s and CD103+ cDC1s originate from pre-committed progenitors influenced by GM-CSF.
  • CD103+ cDC1s differentiate via GM-CSF from pre-cDC1s, while CD301b+ cDC2s arise as cytokine-induced states.
  • Both subsets display enhanced T cell priming and distinct cytokine profiles upon GM-CSF stimulation.
  • GM-CSF signaling within DCs is largely dispensable for CD103/CD301b expression in vivo, except in lung DCs.
  • Type 2 cytokines induce CD103 and CD301b expression ex vivo.

Conclusions:

  • GM-CSF and specific type 2 cytokines are key regulators of cDC1 and cDC2 effector differentiation.
  • CD301b serves as a marker for a cytokine-induced cDC2 state, clarifying cDC heterogeneity.

Keywords:
CD103(+) cDC1CD301bCD301b(+) cDC2CP: immunologyDC2 and DC3 progenitorGM-CSFcell stateconventional dendritic cellsheterogeneityontogenytype 2 cytokines

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