TY - JOUR
T1 - GM-CSF and specific type 2 cytokines induce CD103+and CD301b+cell states in cDC1s and cDC2s
AU - Amon, Lukas
AU - Vurnek, Damir
AU - Seichter, Anna
AU - Tchitashvili, Giorgi
AU - Kaszubowski, Tomasz
AU - Mroz, Markus
AU - Debeuf, Nincy
AU - Vogler, Tina
AU - Küpper, Nicole
AU - Rengarajan, Kaushikk Ravi
AU - Lächele, Lukas
AU - Tochoedo, Nounagnon R.
AU - Baranska, Anna
AU - Autenrieth, Stella E.
AU - Nimmerjahn, Falk
AU - Hildner, Kai
AU - Pfeffer, Klaus
AU - Schraml, Barbara U.
AU - Heger, Lukas
AU - Lambrecht, Bart N.
AU - Lehmann, Christian H.K.
AU - Dudziak, Diana
N1 - Publisher Copyright:
© 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/
PY - 2025/12/23
Y1 - 2025/12/23
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105025654344
U2 - 10.1016/j.celrep.2025.116589
DO - 10.1016/j.celrep.2025.116589
M3 - Article
C2 - 41307996
AN - SCOPUS:105025654344
SN - 2639-1856
VL - 44
JO - Cell Reports
JF - Cell Reports
IS - 12
M1 - 116589
ER -