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

Abstract

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.

Keywords: CD103(+) cDC1; CD301b; CD301b(+) cDC2; CP: immunology; DC2 and DC3 progenitor; GM-CSF; cell state; conventional dendritic cells; heterogeneity; ontogeny; type 2 cytokines.