GM-CSF-dependent CD301b+ mouse lung dendritic cells confer tolerance to inhaled allergens
Christina L. Wilkinson,
Keiko Nakano,
Sara A. Grimm,
Gregory S. Whitehead,
Yukitomo Arao,
Perry J. Blackshear,
Peer W. Karmaus,
Michael B. Fessler,
Donald N. Cook () and
Hideki Nakano ()
Additional contact information
Christina L. Wilkinson: NIH
Keiko Nakano: NIH
Sara A. Grimm: NIH
Gregory S. Whitehead: NIH
Yukitomo Arao: NIH
Perry J. Blackshear: NIH
Peer W. Karmaus: NIH
Michael B. Fessler: NIH
Donald N. Cook: NIH
Hideki Nakano: NIH
Nature Communications, 2025, vol. 16, issue 1, 1-18
Abstract:
Abstract The severity of allergic asthma is driven by the balance between allergen-specific T regulatory (Treg) and T helper (Th)2 cells. However, it is unclear whether specific subsets of conventional dendritic cells (cDCs) promote the differentiation of Tregs. We have identified a subset of lung resident type 2 cDCs (cDC2s) that display high levels of CD301b and have potent Treg-inducing activity ex vivo. Single-cell RNA sequencing and adoptive transfer experiments show that during allergic sensitization, many CD301b+ cDC2s transition in a stepwise manner to CD200+ cDC2s that selectively promote Th2 differentiation. GM-CSF augments the development and maintenance of CD301b+ cDC2s in vivo, and also selectively expands Treg-inducing CD301b+ cDC2s derived from bone marrow. Upon their adoptive transfer to recipient mice, lung-derived CD301b+ cDC2s confer immunological tolerance to inhaled allergens. Thus, GM-CSF maintains lung homeostasis by increasing numbers of Treg-inducing CD301b+ cDC2s.
Date: 2025
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DOI: 10.1038/s41467-025-63547-3
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