RESUMEN
CD45 is a leukocyte-specific tyrosine phosphatase important for T-cell development, and as a result, CD45-/- mice have substantially reduced numbers of T cells. Here we show that, upon dextran sodium sulfate (DSS)-induced colitis, CD45-/- mice have equivalent intestinal pathology and T-cell numbers in their colon as C57BL/6 mice and show enhanced weight loss. CD45-/- mice have a greater percentage of α4ß7+ T cells prior to and after colitis and an increased percentage of T cells producing inflammatory cytokines in the inflamed colon, suggesting that CD45-/- effector T cells preferentially home to the intestine. In DSS-induced colitis in CD45RAG-/- mice lacking an adaptive immune system, CD45 was required for optimal granulocyte-macrophage colony-stimulating factor (GM-CSF) and retinoic acid (RA) production by innate immune cells. Addition of CD45+/+ T cells led to greater weight loss in the RAG-/- mice compared with CD45RAG-/- mice that correlated with reduced α4ß7+ T cells and lower recruitment to the colon of CD45RAG-/- mice in DSS-induced colitis. Addition of exogenous GM-CSF to CD45RAG-/- mice rescued RA production, increased colonic T-cell numbers, and increased weight loss. This demonstrates opposing effects of CD45 in innate and adaptive immune cells in proinflammatory responses and the expression of the gut-homing molecule, α4ß7.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Tretinoina/metabolismo , Animales , Antígenos Ly/metabolismo , Movimiento Celular/genética , Movimiento Celular/inmunología , Colitis/inducido químicamente , Colitis/genética , Colitis/inmunología , Colitis/metabolismo , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Expresión Génica , Inmunidad Innata , Inflamación/inmunología , Inflamación/patología , Mediadores de Inflamación/metabolismo , Intestinos/inmunología , Intestinos/patología , Antígenos Comunes de Leucocito/genética , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Ratones , Ratones Noqueados , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismoRESUMEN
Studies have shown self-weighing behaviour is associated with weight loss and maintenance of previous losses. In this cross-sectional survey of 151 patients, 98 (65.0%) participants were overweight or obese, and 59 (31.9%) participants did not self-weigh. Healthcare teams should advise patients on weighing practices to control obesity.