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

Abstract

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. We investigated the role of the appropriate expression of Bach2 in T cells in the development and prolongation of ACD. 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. 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. The appropriate expression of Bach2 in T cells may be a key factor in the resolution of ACD.