GM-CSF and specific type 2 cytokines induce CD103+ and CD301b+ cell states in cDC1s and cDC2s — ASN Events
  1. Schedule
  2. Plenary 5: DCs in Mucosal Immunity, Homeostasis & Host Defense
  3. GM-CSF and specific type 2 cytokines induce CD103+ and CD301b+ cell states in cDC1s and cDC2s

GM-CSF and specific type 2 cytokines induce CD103+ and CD301b+ cell states in cDC1s and cDC2s (#112)

Lukas Amon 1 , Damir Vurnek 2 , Anna Seichter 3 , Tomasz Kaszubowski 3 , Markus Mroz 4 , Nincy Debeuf 1 , Tina Vogler 5 , Nicole Küpper 6 , Kaushikk Ravi Rengarajan 7 , Lukas Lächele 3 , Nounagnon Romaric Tochoedo 2 , Anna Baranska 3 8 , Stella Autenrieth 9 , Falk Nimmerjahn 10 , Kai Hildner 5 , Klaus Pfeffer 6 , Barbara Schraml 7 , Lukas Heger 3 11 , Bart Lambrecht 1 , Christian H.K. Lehmann 3 12 , Diana Dudziak 2
  1. Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium
  2. Universitätsklinikum Jena, Jena, THURINGIA, Germany
  3. Laboratory of DC-Biology, University Hospital Erlangen, Erlangen, Germany
  4. Core Unit Cell Sorting and Immunomonitoring, University Hospital Erlangen, Erlangen, Germany
  5. Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany
  6. Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Duesseldorf, Düsseldorf, Germany
  7. Institute for Immunology, Biomedical Center Munich, LMU Munich, Munich, Germany
  8. Miltenyi Biotec B.V. & Co. KG, Miltenyi , Bergisch-Gladbach, Germany
  9. Dendritic Cells in Infection and Cancer (D431), German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany
  10. Division of Genetics, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany
  11. Department of Transfusion Medicine and Haemostaseology, University Hospital Erlangen, Erlangen, Germany
  12. Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany

Our laboratory is interested in understanding the heterogeneity of conventional dendritic cells type 1 (cDC1s) and type 2 (cDC2s). Still, 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-CSFdriven 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. 

This study was partly funded via ANR/DFG (DU548/6-1) and TRR305-B05.