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

doi:10.1016/j.jaci.2025.01.036

Loss of Bach2 in T cells causes prolonged allergic inflammation through accumulation of effector T cells and disruption of epidermal barrier

J Allergy Clin Immunol. 2025 Feb 7:S0091-6749(25)00128-9. doi: 10.1016/j.jaci.2025.01.036. Online ahead of print.

Authors

Miyuki Omori-Miyake¹, Ryosuke Kawakami², Makoto Kuwahara³, Masataka Okabe⁴, Jun Muto⁵, Takeshi Imamura², Masakatsu Yamashita⁶

Affiliations

¹ Department of Infections and Host Defenses, Ehime University Graduate School of Medicine, Ehime, Japan.
² Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Ehime, Japan.
³ Department of Immunology, Ehime University Graduate School of Medicine, Ehime, Japan.
⁴ Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.
⁵ Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
⁶ Department of Infections and Host Defenses, Ehime University Graduate School of Medicine, Ehime, Japan; Department of Immunology, Ehime University Graduate School of Medicine, Ehime, Japan. Electronic address: yamamasa@m.ehime-u.ac.jp.

PMID: 39924123
DOI: 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.

Keywords: Allergic contact dermatitis; Bach2; T cell; eczema.