title: Clinical perspectives and murine models of lichenoid tissue reaction/interface dermatitis.
abstract: 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.
authors: Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan. Electronic address: naoko.okiyama@md.tsukuba.ac.jp.
authors: Naoko
authors: N
authors: Okiyama
authors: Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.
authors: Manabu
authors: M
authors: Fujimoto
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D003872:Dermatitis / Q000276:immunology* / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D015603:Keratinocytes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D017512:Lichenoid Eruptions / Q000276:immunology* / Q000628:therapy; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D051193:Toll-Like Receptors
keywords: Cytotoxic T cells; Drug eruption; Graft-versus-host disease; Keratinocyte death; Lichen planus; Lupus erythematosus