GM-CSF and specific type 2 cytokines induce CD103+ and CD301b+ cell states in cDC1s and cDC2s
The heterogeneity of conventional dendritic cells type 1 (cDC1s) and type 2 (cDC2s) is well established, yet the identity and origin of CD301b<sup>+</sup> cDC2s remain debated. Here, we show that CD301b<sup>+</sup> cDC2s and CD103<sup>+</sup> cDC1s develop from pre-committed progenitors in response to granulocyte/macrophage colony-stimulating factor (GM-CSF). While CD103<sup>+</sup> cDC1s acquire their phenotype and functional properties through GM-CSF-driven differentiation from pre-cDC1s, CD301b<sup>+</sup> cDC2s emerge as cytokine-induced states from DC2- and DC3-committed progenitors. CD103<sup>+</sup> cDC1s and CD301b<sup>+</sup> cDC2s exhibit enhanced T cell priming capacities and distinct cytokine expression profiles upon GM-CSF exposure. In vivo, DC-intrinsic GM-CSF sensing is dispensable for acquiring CD103 and CD301b expression with the notable exception of lung DCs, while specific type 2 cytokines induce CD103 and CD301b ex vivo. These findings identify GM-CSF and specific type 2 cytokines as central regulators of cDC1 and cDC2 effector differentiation and establish CD301b as a marker of a cytokine-driven cDC2 state.
Authors
- Nicole Küpper
- Nounagnon Romaric Tochoedo
- Tina Vogler
- Kai Hildner (ORCID: https://orcid.org/0000-0001-5007-4874)
- Damir Vurnek
- Lukas Heger (ORCID: https://orcid.org/0000-0001-5591-2187)
- Anna Seichter (ORCID: https://orcid.org/0009-0005-4339-4104)
- Stella E. Autenrieth (ORCID: https://orcid.org/0000-0003-4054-9041)
- Nincy Debeuf (ORCID: https://orcid.org/0000-0002-4754-4772)
- Tomasz Kaszubowski (ORCID: https://orcid.org/0009-0000-6453-5969)
- Anna Barańska (ORCID: https://orcid.org/0000-0003-4140-1233)
- Barbara U. Schraml (ORCID: https://orcid.org/0000-0002-5801-0151)
- Giorgi Tchitashvili
- Klaus Pfeffer (ORCID: https://orcid.org/0000-0002-5652-6330)
- Lukas Amon (ORCID: https://orcid.org/0000-0003-3834-6114)
- Diana Dudziak (ORCID: https://orcid.org/0000-0001-9358-134X)
- Christian H.K. Lehmann (ORCID: https://orcid.org/0000-0001-5927-9761)
- Bart N. Lambrecht (ORCID: https://orcid.org/0000-0003-4376-6834)
- Falk Nimmerjahn (ORCID: https://orcid.org/0000-0002-5418-316X)
- Lukas Lächele
- Markus Mroz
- K Rengarajan (ORCID: https://orcid.org/0009-0001-4829-6117)
Institutions
- German Cancer Research Center (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Heidelberg University (DE)
- Universitätsklinikum Erlangen (DE)
- German Cancer Society (DE)
- Jena University Hospital (DE)
- Bernstein Center for Computational Neuroscience Munich (DE)
- VIB-UGent Center for Inflammation Research (BE)
- Comprehensive Cancer Center Erlangen (DE)
- DKFZ-ZMBH Alliance (DE)
- Heinrich Heine University Düsseldorf (DE)
- Friedrich Schiller University Jena (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1016/j.celrep.2025.116589
- Citations
- 1
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Universitätsklinikum Jena
- Servier