A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses.

The pleiotropic alarmin interleukin-33 (IL-33) drives type 1, type 2 and regulatory T-cell responses via its receptor ST2. Subset-specific differences in ST2 expression intensity and dynamics suggest that transcriptional regulation is key in orchestrating the context-dependent activity of IL-33-ST2 signaling in T-cell immunity. Here, we identify a previously unrecognized alternative promoter in mice and humans that is located far upstream of the curated ST2-coding gene and drives ST2 expression in type 1 immunity. Mice lacking this promoter exhibit a selective loss of ST2 expression in type 1- but not type 2-biased T cells, resulting in impaired expansion of cytotoxic T cells (CTLs) and T-helper 1 cells upon viral infection. T-cell-intrinsic IL-33 signaling via type 1 promoter-driven ST2 is critical to generate a clonally diverse population of antiviral short-lived effector CTLs. Thus, lineage-specific alternative promoter usage directs alarmin responsiveness in T-cell subsets and offers opportunities for immune cell-specific targeting of the IL-33-ST2 axis in infections and inflammatory diseases.

Tratamiento conservador de la osteoartrosis de cadera con toxina botulínica tipo A / Conservative treatment of hip osteoarthritis with botulinum toxin type A

Resumen Introducción: La osteoartritis de cadera es una enfermedad articular inflamatoria de bajo grado y etiología múltiple que tiene un manejo conservador limitado y poco explorado. La aplicación de toxina botulínica tipo A (BoNT-A) produce en el músculo aplicado una parálisis flácida temporal, delimitable y reversible, que aplicada de manera estratégica logra liberar estrés mecánico y dolor Objetivo: Evaluar el efecto en la percepción de dolor, funcionalidad y rigidez y los cambios en la flexión, rotación interna y externa, antes y 90 días después de la aplicación de BoNT-A. Métodos: Estudio clínico, experimental, longitudinal, abierto, con un total de 35 pacientes y 45 caderas tratadas. Se aplicó BoNT-A de 500 U en músculos ilíaco, músculo aductorbrevis y longus. Resultados: Se utilizó la prueba de Wilcoxon comparando los puntajes de evaluación en los días 0 a 90 observando disminución significativa del dolor referido (p < 0.0001), rigidez (p < 0.002), mejoró la función percibida (p < 0.001) y los arcos de movilidad: flexión, rotación interna y externa (p < 0.0001). Conclusiones: El tratamiento con BoNT-A otorga una opción conservadora y segura para el manejo de los síntomas y restricción física causada por la OA de cadera.

Abstract Introduction: Osteoarthritis (OA) of the hip is a low-grade inflammatory disease of multiple etiology that has a limited conservative management and insufficiently explored. The application of botulinum toxin type A (BoNT-A) produces in the applied muscle a temporary, delimitable and reversible flaccid paralysis, which applicated in a strategic way achives to reduce mechanical stress and pain. Objective: To evaluate the effect on pain perception, functionality and rigidity and changes in flexibility, internal and external rotation, before and 90 days after the application of BoNT-A. Methods: Clinical, experimental, longitudinal, open study, with a total of 35 patients and 45 hips treated. BoNT-A of 500 U was applied in iliac, adductor brevis and longus muscles. Results: The Wilcoxon test was used to compare the evaluation scores on days 0-90, observing the decrease in referred pain (p < 0.0001), rigidity (p < 0.002), improved perceived function (p < 0.001) and mobility arcs: flexion, internal and external rotation (p < 0.0001). Conclusions: The treatment with BoNT-A provides a conservative and safe option for the management of symptoms and physical restraint caused by hip OA.