Selective regulation in expression of co-inhibitory molecule B7-H1/PD-L1 on masticatory mucosae

[Purpose] Oral mucosae are covered by stratified squamous epithelia and possess multiple functions as epithelial barrier, masticatory mucosa, and permeabilization. Especially, oral masticatory mucosae receive various dietary and microbial stimuli, they might have protective mechanisms to avoid excess immune responses. B7-H1/PD-L1 (CD274) is one of ligands for co-inhibitory receptor PD-1 (CD279). It’s often induced on non-lymphoid tissue cells at the inflammatory condition and B7-H1:PD-1 pathway negatively regulates T cell activation. In this study, we examined expression and regulation of B7-H1 in mouse epithelia. [Results and Discussion] B7-H1 was physiologically induced on prickle cells, but not basal cells of masticatory mucosae including dorsal surface of tongue (DST), gingiva, and hard palate. Expression levels were age-relatedly increased, epithelium of non-masticatory oral mucosae and other organs and skin never express B7-H1 in the steady state. Topical painting TPA, DNFB, and OVA on the skin, buccal mucosa (BM), and DST induced activation and proliferation of basal cells assessed by Ki67 expression and induced B7-H1 on both prickle and basal cells. However, the enhanced B7-H1 levels on basal cells of BM and DST were clearly impaired. In OVA-primed DO11.10 T cell-transferred mice, blockade of B7-H1 at the time of topical OVA/DNFB painting on DST dramatically enhanced mucosal inflammation assessed by increased mononuclear cell infiltration and MHC class II expression, suggesting protective roles of B7-H1. Basal cells in masticatory mucosae have conflicting roles; to protect from microbial infection and to maintain metabolism of the epithelium, therefore, B7-H1 expression in the basal cells may be strictly regulated.