The presence of T cells with low-levels of Bach2 contributes to the worsening and/or prolongation of allergic dermatitis symptoms

The research group led by Drs. Miyuki Omori-Miyake and Masakatsu Yamashita has discovered that Bach2, a protein essential for regulating T cells function, plays a crucial role in the remission of atopic dermatitis symptoms. These findings suggest that modulating Bach2 levels in T cells may provide a potential strategy to prevent the progression the pathogenesis of atopic dermatitis.

Atopic dermatitis is an allergy affecting approximately 10% of the Japanese population, with symptoms closely related to social stress. In socially active adults, the disease often becomes chronic. In affected areas, infiltrating immune cells secrete inflammatory cytokines, which contribute to symptom development. While these cytokines normally play a protective role against pathogenic microbes under physiological conditions, their excessive and prolonged release in atopic dermatitis disrupts the epidermal barrier – the skin’s first line of defense against environmental factors. The inflammatory responses in atopic dermatitis are initially triggered by T cells, followed by other immune and tissue cells.
Our research group has been conducting fundamental studies aimed at addressing the pathogenesis of allergies by precisely regulating T-cell function. In this study, we focused on Bach2, a protein essential for maintaining normal T-cell function. To investigate its role in atopic dermatitis, we generated three types of mouse models: mice in which Bach2 levels can be monitored using a fluorescent tag, transgenic mice with T cells expressing high levels of Bach2 (Bach2 Tg mice) and knockout mice lacking Bach2 in T cells (Bach2 KO mice).
The key findings of this study were: (1) T cells with low and/or intermediate levels of Bach2 accumulate in the affected areas of atopic dermatitis; (2) Bach2 Tg mice do not develop atopic dermatitis, whereas Bach2 KO mice exhibit severe and prolonged (chronic) symptoms (Figure1); (3) Bach2 KO mice have a more fragile skin barrier, both functionally and structurally (Figure2).
Bach2 levels are dynamically regulated along with T-cell status. The findings of this study suggest that precise modulation of Bach2 levels in T cells may help reduce the chronicity of atopic dermatitis, highlighting the potential for developing a novel therapeutic approach targeting Bach2 regulation in T cells.

Reference URL: https://doi.org/10.1016/j.jaci.2025.01.036

Bibliographic Information

Loss of Bach2 in T cells causes prolonged allergic inflammation through accumulation of effector T cells and disruption of epidermal barrier,
Miyuki Omori-Miyake, Ryosuke Kawakami,
Makoto Kuwahara, Masataka Okabe, Jun Muto, Takeshi Imamura, Masakatsu Yamashita,
Journal of Allergy and Clinical Immunology, in press,
doi: 10.1016/j.jaci.2025.01.036, 2025 (February 7).

Fundings

• Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number 23H02736, 22K08433, 21K08205)
• the Takeda Science Foundation, the Hoyu Science Foundation, the Naito Science & Engineering Foundation

Media

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  Area of skin where experimental atopy-like dermatitis was induced

  Compared to control mice, Bach2 KO mice exhibit exacerbated dermatitis, whereas Bach2 Tg mice remain unaffected.

  credit : Drs. Miyuki Omori-Miyake and Masakatsu Yamashita (Ehime University)
  Usage Restriction : Please get copyright permission

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  Outline of the findings of our present research

  The accumulation of T cells with low Bach2 levels disrupts the epidermal barrier, weakening epidermal structures and promotes tissue fibrosis, resulting in the loss of normal tissue function. Proper regulation of Bach2 levels in T cells may help resolve atopic dermatitis symptoms, prevent chronic inflammation and skin barrier disruption and reduce the risk of disease development.

  credit : Drs. Miyuki Omori-Miyake and Masakatsu Yamashita (Ehime University)
  Usage Restriction : Please get copyright permission