2026-08-07 九州大学
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1551
- https://www.sciencedirect.com/science/article/pii/S0168365926004621
代謝可能なAhRアゴニストを搭載したナノ粒子を用いた、抗原特異的免疫調節のための、B細胞を標的とした一時的な寛容スイッチ A transient, B cell–targeted tolerance switch using nanoparticles loaded with metabolizable AhR agonists for antigen-specific immune regulation
Takanatsu Hosokawa, Takuro Yamada, Gyeongwoo Lee, Kengo Hamamura, Yuya Yoshida, Daisuke Takahashi, Teruki Nii, Akihiro Kishimura, Daisuke Murakami, Naoya Matsunaga, Koji Hase, Yoshiki Katayama, Yoshihiro Baba, Takeshi Mori
Journal of Controlled Release Available online: 28 May 2026
DOI:https://doi.org/10.1016/j.jconrel.2026.115059
Highlights
- Nanoparticles loaded with metabolizable AhR agonists induce IL-10–producing regulatory B cells (Bregs).
- Bregs directly present antigen and induce antigen-specific regulatory T cells.
- Time-gated tolerance is achieved only during antigen co-exposure via rapid drug metabolism.
- B-cell and dendritic cell functions are preserved, avoiding systemic immunosuppression.
- Co-administration with antigen suppresses anti-drug antibody formation and allergic inflammation in mouse models.
Abstract
Achieving antigen-specific immune tolerance without systemic immunosuppression remains a major challenge in biomaterial-based immunotherapy. Here, we report a simple nanoparticle (NP)-based platform that enables a transient, B cell–targeted tolerance switch. NPs encapsulating metabolizable aryl hydrocarbon receptor (AhR) agonists—FICZ or ITE—preferentially accumulate in splenic marginal zone B cells and convert them into IL-10–producing regulatory B cells (Bregs). This study provides the first in vivo evidence that Bregs can directly present antigen and induce regulatory T cells (Tregs), establishing a NP-controlled Breg–Treg pathway. These Bregs promote antigen-specific Tregs expansion only when co-exposed to antigen, establishing time-gated, antigen-restricted immune regulation. By exploiting the rapid metabolism of AhR agonists, this system provides precise temporal control of tolerance induction while preserving vaccine responses. In mouse models, co-administration of FICZ-containing NP with antigen suppressed anti-drug antibody formation and ameliorated allergic inflammation. This NP platform demonstrates a strategy for safe, antigen-specific immunomodulation and offers a clinically adaptable framework for allergy and biotherapeutic tolerance.
