GM-CSF derived from alveolar type 2 cells promotes CD301b + cDC2 generation and allergic airway inflammation
Year: 2025
Type: article
Abstract: 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 + subset of terminally differentiated cDC2s, in addition to CD103 + XCR1 + cDC1s. Unbiased single-cell transcriptomic profiling of CD11c + cells identified both immature and differentiated lung cDC populations. GM-CSF deficiency disrupted antiapoptotic Bcl2a1 up-regulation and impaired progression to the CD301b + transcriptional state. Despite the positioning of CD301b + 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 + cDC2 formation and pulmonary type 2 immune responses, highlighting the central role of GM-CSF signaling in shaping the pulmonary myeloid landscape.
Source: Science Immunology
Authors: Julia Gschwend, Antonie Lechner, Nikolaos D. Sidiropoulos, Paul Maier, Tilde Andersson, Flurin Sturzenegger, Basak Corak, Nina Brander, David A. Bejarano, Elina Wells, Sandra P. Melo, Joana R. D. Martins, Maximilian Nitschké, Ari B. Molofsky, Andreas Schlitzer, Isabelle C. Arnold, Sarah Mundt, Burkhard Becher, Manfred Kopf, Hubert Rehrauer, Christoph Schneider
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4413055376