Lukas Amon, Damir Vurnek, Anna Seichter, Giorgi Tchitashvili, Tomasz Kaszubowski, Markus Mroz, Nincy Debeuf, Tina Vogler, Nicole Küpper, K Rengarajan, Lukas Lächele, Nounagnon Romaric Tochoedo, Anna Barańska, Stella E. Autenrieth, Falk Nimmerjahn, Kai Hildner, Klaus Pfeffer, Barbara U. Schraml, Lukas Heger, Bart N. Lambrecht, Christian H.K. Lehmann, Diana Dudziak
The heterogeneity of conventional dendritic cells type 1 (cDC1s) and type 2 (cDC2s) is well established, yet the identity and origin of CD301b + cDC2s remain debated. Here, we show that CD301b + cDC2s and CD103 + cDC1s develop from pre-committed progenitors in response to granulocyte/macrophage colony-stimulating factor (GM-CSF). While CD103 + cDC1s acquire their phenotype and functional properties through GM-CSF-driven differentiation from pre-cDC1s, CD301b + cDC2s emerge as cytokine-induced states from DC2- and DC3-committed progenitors. CD103 + cDC1s and CD301b + 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.