title: Unique B7-H1 expression on masticatory mucosae in the oral cavity and trans-coinhibition by B7-H1-expressing keratinocytes regulating CD4+T cell-mediated mucosal tissue inflammation.
abstract: The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated. B7-H1 on prickle cells was upregulated by external topical stimuli, but B7-H1 on basal KCs was induced only by internal stimuli via infiltrating cells. The blocking of KC-associated B7-H1 or the lack of programmed cell death-1 (PD-1) on tissue effector CD4+T cells in mice lacking B7-H1 on immune cells drastically exacerbated the tissue inflammation induced by topical OVA painting as an exogenous antigen, indicating direct interaction with KCs and CD4+T cells. Trans-coinhibitory signals by KCs may modulate local T-cell/dendritic cell activation, resulting in inhibition of T-cell responses in both peripheral and secondary lymphoid tissues. Careful control of B7-H1 induction in KCs may play a crucial role in the protection from CD4+T cell-mediated tissue inflammation by exogenous antigens delivered from the mucosal surface.
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Azuma
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009055:Mouth / Q000276:immunology*; D009061:Mouth Mucosa / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D013284:Stomatognathic System / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor