A Phenotypic Analysis of Involucrin-Membrane-Bound Ovalbumin Mice after Adoptive Transfer of Ovalbumin-Specific CD8⁺ T Cells

To investigate the mechanism of autoimmunity and peripheral tolerance in the skin, several transgenic mouse strains expressing membrane-bound ovalbumin (mOVA) as an epidermal self-antigen under the control of keratinocyte-specific promotors, such as keratin 5 and keratin 14, were employed in combination with adoptive transfer of CD8⁺ T cells from OT-I mice (OT-I T cells) that recognize an ovalbumin-derived peptide. However, these strains showed bodyweight loss and required additional inflammatory stimuli, such as γ-irradiation and tape-stripping, to induce skin inflammation. In this study, we generated a mouse strain expressing mOVA under the control of human involucrin promoter (involucrin-mOVA mice). In contrast to previous strains, involucrin-mOVA mice spontaneously developed skin inflammation after the transfer of OT-I T cells in the absence of external stimuli without significant bodyweight loss. We focused on the skin infiltration process of OT-I T cells and found that transferred OT-I T cells accumulated around the hair follicles in the early phase of skin inflammation, and in the later phase, the skin inflammation spontaneously resolved despite the remaining OT-I T cells in the skin. Our involucrin-mOVA mice will provide a promising tool to investigate the pathogenesis and the tolerance mechanisms of cytotoxic skin autoimmunity

Effects of Motilin Receptor Agonists and Ghrelin in Human <i>motilin receptor</i> Transgenic Mice

Gastrointestinal motility is regulated by neural factors and humoral factors. Both motilin and ghrelin improve gastrointestinal motility, but many issues remain unclear. We prepared human motilin receptor transgenic (Tg) mice and performed experiments evaluating the effects of motilin, erythromycin (EM), and ghrelin. EM and ghrelin promoted gastric emptying (GE) when administered either peripherally or centrally to Tg mice. Atropine (a muscarinic receptor antagonist) counteracted GE induced by centrally administered EM, but not that induced by peripherally administered EM. The administration of EM in this model promoted the effect of mosapride (a selective serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist), and improved loperamide (a &#956;-opioid receptor agonist)-induced gastroparesis. The level of acyl-ghrelin was significantly attenuated by EM administration. Thus, we have established an animal model appropriate for the evaluation of motilin receptor agonists. These data and the model are expected to facilitate the identification of novel compounds with clinical potential for relieving symptoms of dyspepsia and gastroparesis