GM-CSF derived from alveolar type 2 cells promotes CD301b <sup>+</sup> cDC2 generation and allergic airway inflammation
Pulmonary conventional dendritic cells (cDCs) are functionally and phenotypically heterogeneous antigen-presenting cells essential for orchestrating adaptive immune responses in the lung. Here, we define a cell-intrinsic role for granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling in the development of a CD301b<sup>+</sup> subset of terminally differentiated cDC2s, in addition to CD103<sup>+</sup>XCR1<sup>+</sup> cDC1s. Unbiased single-cell transcriptomic profiling of CD11c<sup>+</sup> cells identified both immature and differentiated lung cDC populations. GM-CSF deficiency disrupted antiapoptotic Bcl2a1 up-regulation and impaired progression to the CD301b<sup>+</sup> transcriptional state. Despite the positioning of CD301b<sup>+</sup> cDC2s in lymphoid cell-rich adventitial cuff areas, hematopoietic GM-CSF was dispensable for their development. Instead, alveolar epithelial type 2 cell-derived GM-CSF was required for CD301b<sup>+</sup> cDC2 formation and pulmonary type 2 immune responses, highlighting the central role of GM-CSF signaling in shaping the pulmonary myeloid landscape.
Authors
- Paul Maier (ORCID: https://orcid.org/0000-0001-6606-3926)
- Hubert Rehrauer (ORCID: https://orcid.org/0000-0001-7612-9394)
- Antonie Lechner (ORCID: https://orcid.org/0000-0002-1636-3354)
- Sarah Mundt (ORCID: https://orcid.org/0000-0003-2169-2109)
- Nikolaos D. Sidiropoulos (ORCID: https://orcid.org/0000-0003-3257-3455)
- David Alejandro Bejarano (ORCID: https://orcid.org/0000-0001-7804-0131)
- Basak Corak (ORCID: https://orcid.org/0000-0002-8255-9793)
- Julia Gschwend (ORCID: https://orcid.org/0000-0001-7212-4393)
- Burkhard Becher (ORCID: https://orcid.org/0000-0002-1541-7867)
- Tilde Andersson (ORCID: https://orcid.org/0000-0001-8168-5002)
- Sandra P. Melo
- Ari B. Molofsky (ORCID: https://orcid.org/0000-0003-0764-3175)
- Joana Raquel Martins (ORCID: https://orcid.org/0000-0002-3784-9775)
- Christoph Schneider (ORCID: https://orcid.org/0000-0002-0452-2960)
- Isabelle C. Arnold (ORCID: https://orcid.org/0000-0001-8679-9666)
- Maximilian Nitschké
- Flurin Sturzenegger (ORCID: https://orcid.org/0009-0000-1306-6605)
- Manfred Köpf (ORCID: https://orcid.org/0000-0002-0628-7140)
- Andreas Schlitzer (ORCID: https://orcid.org/0000-0001-7662-3712)
- Nina Brander
- E. Wells
Institutions
- University of Bonn (DE)
- University of California, San Francisco (US)
- University of Zurich (CH)
- Genesys (United States) (US)
- ETH Zurich (CH)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-08-08
- DOI
- https://doi.org/10.1126/sciimmunol.adt0688
- Citations
- 3
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 2.39