アトピー性皮膚炎が慢性化にいたるメカニズムを発見～T細胞を標的とした治療法開発に期待～

2025-03-27 愛媛大学

<関連情報>

• https://www.ehime-u.ac.jp/data_relese/pr_20250327_med/
• https://www.ehime-u.ac.jp/wp-content/uploads/2025/03/pr_20250327_med.pdf
• https://www.jacionline.org/article/S0091-6749(25)00128-9/fulltext

T細胞におけるBach2の欠損は、エフェクターT細胞の蓄積と表皮バリアの破壊を通じてアレルギー性炎症の長期化を引き起こす Loss of Bach2 in T cells causes prolonged allergic inflammation through accumulation of effector T cells and disruption of epidermal barrier

Miyuki Omori-Miyake, PhD ∙ Ryosuke Kawakami, PhD ∙ Makoto Kuwahara, PhD∙ … ∙ Jun Muto, MD, PhD ∙ Takeshi Imamura, MD, PhD ∙ Masakatsu Yamashita, PhD
The Journal of Allergy and Clinical Immunology  Published:February 7, 2025
DOI:https://doi.org/10.1016/j.jaci.2025.01.036

Abstract

Background
Bach2 has been suggested to be a risk factor for allergic diseases in previous studies. Because type IV hypersensitivity reactions, including allergic contact dermatitis (ACD), develop through activated T cells, and because the expression of Bach2 is regulated in the development and functional differentiation of T cells, the expression of Bach2 in T cells may be involved in the onset of ACD. However, the role of Bach2 in T cells during ACD development has not yet been determined.

Objective
We investigated the role of the appropriate expression of Bach2 in T cells in the development and prolongation of ACD.

Methods
We induced ACD in mice by repeatedly applying a hapten and analyzed the expression of Bach2 in the T cells of lesional skin or skin-draining lymph nodes (sdLNs). We performed a phenotypic analysis of the skin and/or sdLNs by comparing mice with T cells overexpressing Bach2 or with Bach2 loss to the control mice.

Results
We found that Bach2^lo T cells accumulated in the skin and sdLNs as ACD developed. T-cell–specific Bach2-deficient mice showed more severe inflammatory responses to the hapten and had prolonged inflammation with T cells expressing higher levels of IL-13 in the skin and IFN-γ and IL-13 in the sdLNs. In contrast, the mice overexpressing Bach2 in T cells developed almost no symptoms of ACD.

Conclusion
The appropriate expression of Bach2 in T cells may be a key factor in the resolution of ACD.