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
- Hideki Nakano
2025-09-29
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.