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<p>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<sup>+</sup> cDC2s transition in a stepwise manner to CD200<sup>+</sup> cDC2s that selectively promote Th2 differentiation. GM-CSF augments the development and maintenance of CD301b<sup>+</sup> cDC2s in vivo, and also selectively expands Treg-inducing CD301b<sup>+</sup> cDC2s derived from bone marrow. Upon their adoptive transfer to recipient mice, lung-derived CD301b<sup>+</sup> cDC2s confer immunological tolerance to inhaled allergens. Thus, GM-CSF maintains lung homeostasis by increasing numbers of Treg-inducing CD301b<sup>+</sup> cDC2s.</p>

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GM-CSF-dependent CD301b+ mouse lung dendritic cells confer tolerance to inhaled allergens

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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  • 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

摘要

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.