RESUMEN
The potent and partial agonist sunobinop activates the nociceptin/orphanin-FQ peptide receptor and promotes non-REM sleep in rodents and patients with insomnia.
Asunto(s)
Nociceptina , Trastornos del Inicio y del Mantenimiento del Sueño , Animales , Humanos , Receptores Opioides/agonistas , Receptores Opioides/fisiología , Péptidos Opioides , Receptor de Nociceptina , Roedores , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , SueñoRESUMEN
The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR alpha-chain knockout mice and IL-7 transgenic mice. Transfer of mucosal T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2(-/-) mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.