Clinical perspectives and murine models of lichenoid tissue reaction/interface dermatitis

• Keratinocyte death defines lichenoid tissue reaction (LTR)/interface dermatitis (IFD).
• Mucocutaneous diseases with LTR/IFD include drug eruption, GVHD and lupus.
• Clinical findings suggested that cytotoxic T cells mainly mediate LTR/IFD.
• Useful murine models of LTR/IFD have been generated to develop new drugs.

A set of histopathological elements, that is death of epidermal basal cell layer keratinocytes and inflammatory cell infiltration, distinguishes lichenoid tissue reaction (LTR)/interface dermatitis (IFD) from other inflammatory mucocutaneous diseases with histological findings of superficial perivascular dermatitis. The LTR/IFD is observed in inflammatory mucocutaneous diseases such as lichen planus, Stevens–Johnson syndrome/toxic epidermal necrolysis, acute graft-versus-host disease, lupus erythematosus and dermatomyositis. Clinical and basic researches have suggested that keratinocytes are antigen-presenting cells and mediate LTR/IFD reaction via production of cytokines/chemokines and inhibitory molecules such as programmed cell death (PD)-L1, and that cytotoxic CD8+ T cells producing cytotoxic granules, perforin, granzyme B and granulysin are final effector cells to cause keratinocyte death. Because interferon-γ and FasL, which are produced by not only CD8+ but also CD4+ T cells, are candidates of the pathogenic molecules in LTR/IFD, CD4+ T cells may also play a role to develop LTR/IFD. On the other hand, CD4+ Treg cells accelerate the remission of LTR/IFD. Some murine models of LTR/IFD have been established. For example, LTR/IFD reactions were induced in keratinocyte-specific membrane-binding ovalbumin-transgenic (mOVA Tg) mice by adoptive transfer of CD8+ T cells with OVA-specific T-cell-receptor. It has also been shown that human CD8+ T cells are pathogenic immune cells in human skin-xenografted mice. Various immunosuppressants are used to treat patients with mucocutaneous diseases with LTR/IFD. By analysis of the mOVA Tg mice, a JAK inhibitor was suggested to be a new candidate drug to inhibit not only pathogenic T cells but also keratinocyte death in LTR/IFD. More specific treatments for patients with LTR/IFD will be developed in future.