RESUMO
The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4+ T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers. Importantly, ex vivo depletion of dopamine from DCs resulted in a dramatic reduction of EAE severity, highlighting the relevance of an autocrine loop promoting inflammation in vivo. Mechanistic analyses indicated that DRD5-signalling in both mouse DCs and human monocytes involves the attenuation of signal transducer and activator of transcription 3-activation, a transcription factor that limits the production of the inflammatory cytokines interleukin (IL)-12 and IL-23. Furthermore, we found an exacerbated expression of all dopamine receptors in peripheral blood pro-inflammatory monocytes obtained from MS patients. These findings illustrate a novel mechanism by which myeloid antigen-presenting cells may trigger the onset of their inflammatory behaviour promoting the development of autoimmunity.
Assuntos
Células Dendríticas/imunologia , Dopamina/imunologia , Encefalomielite Autoimune Experimental/imunologia , Monócitos/imunologia , Esclerose Múltipla/imunologia , Fator de Transcrição STAT3/imunologia , Adulto , Animais , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Dopamina/metabolismo , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Monócitos/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Receptores de Dopamina D5/genética , Receptores de Dopamina D5/imunologia , Receptores de Dopamina D5/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismoRESUMO
INTRODUCTION: Vesico-ureteral reflux (VUR) is defined as the retrograde flow of urine from the bladder to the upper urinary tract and is distinguished in primary and secondary. It is present in 25-70% of children who have a urinary tract infection (UTI) associated with pyelonephritis, the association between UTI and VUR predisposes children to have renal scarring with consequent alteration of the functionality until chronic renal failure. MATERIAL AND METHODS: We realized a review of the literature on the endoscopic treatment of vesico-ureteral reflux analyzing the different techniques, materials used for endoscopic injection, indications and complications described in the literature. RESULTS: Over 100 articles we found on the endoscopic treatment of reflux with indications, complications and outcomes in the short, medium and long term. Of these we selected the most recent and current European and American Guidelines. CONCLUSIONS: Endoscopic treatment of reflux has become gradually the technique of choice for the primary treatment of vesico-ureteral reflux associated with pyelonephritis or urinary tract infections and permits to delay the use of open surgery.
Assuntos
Cistoscopia , Ureteroscopia , Refluxo Vesicoureteral/cirurgia , Criança , HumanosRESUMO
El refujo vesicoureteral (RVU) es el fujo de orina desde la vejiga hasta el tracto urinario superior. Está presente en el 25% al 70% de los niños con infección urinaria asociada a pielonefritis. Se realizó una revisión de la bibliografía sobre el tratamiento endoscópico del RVU analizando las técnicas, los materiales utilizados, las indicaciones y las complicaciones descritas. De los artículos encontrados, se seleccionaron los más recientes y las Guías Europeas y Norteamericanas. El tratamiento endoscópico del refujo, que se ha impuesto progresivamente como técnica de elección para el tratamiento primario del RVU asociado a pielonefritis o a infecciones, permite retrasar el recurso a la cirugía.
Introduction. Vesico-ureteral refux (VUR) is defned as the retrograde fow of urine from the bladder to the upper urinary tract and is distinguished in primary and secondary. It is present in 25-70% of children who have a urinary tract infection (UTI) associated with pyelonephritis, the association between UTI and VUR predisposes children to have renal scarring with consequent alteration of the functionality until chronic renal failure. Material and methods. We realized a review of the literature on the endoscopic treatment of vesico-ureteral refux analyzing the different techniques, materials used for endoscopic injection, indications and complications described in the literature. Results. Over 100 articles we found on the endoscopic treatment of refux with indications, complications and outcomes in the short, medium and long term. Of these we selected the most recent and current European and American Guidelines. Conclusions. Endoscopic treatment of refux has become gradually the technique of choice for the primary treatment of vesico-ureteral refux associated with pyelonephritis or urinary tract infections and permits to delay the use of open surgery.
Assuntos
Criança , Humanos , Cistoscopia , Ureteroscopia , Refluxo Vesicoureteral/cirurgiaRESUMO
El refujo vesicoureteral (RVU) es el fujo de orina desde la vejiga hasta el tracto urinario superior. Está presente en el 25% al 70% de los niños con infección urinaria asociada a pielonefritis. Se realizó una revisión de la bibliografía sobre el tratamiento endoscópico del RVU analizando las técnicas, los materiales utilizados, las indicaciones y las complicaciones descritas. De los artículos encontrados, se seleccionaron los más recientes y las Guías Europeas y Norteamericanas. El tratamiento endoscópico del refujo, que se ha impuesto progresivamente como técnica de elección para el tratamiento primario del RVU asociado a pielonefritis o a infecciones, permite retrasar el recurso a la cirugía.(AU)
Introduction. Vesico-ureteral refux (VUR) is defned as the retrograde fow of urine from the bladder to the upper urinary tract and is distinguished in primary and secondary. It is present in 25-70% of children who have a urinary tract infection (UTI) associated with pyelonephritis, the association between UTI and VUR predisposes children to have renal scarring with consequent alteration of the functionality until chronic renal failure. Material and methods. We realized a review of the literature on the endoscopic treatment of vesico-ureteral refux analyzing the different techniques, materials used for endoscopic injection, indications and complications described in the literature. Results. Over 100 articles we found on the endoscopic treatment of refux with indications, complications and outcomes in the short, medium and long term. Of these we selected the most recent and current European and American Guidelines. Conclusions. Endoscopic treatment of refux has become gradually the technique of choice for the primary treatment of vesico-ureteral refux associated with pyelonephritis or urinary tract infections and permits to delay the use of open surgery.(AU)
Assuntos
Criança , Humanos , Cistoscopia , Ureteroscopia , Refluxo Vesicoureteral/cirurgiaRESUMO
INTRODUCTION: Vesico-ureteral reflux (VUR) is defined as the retrograde flow of urine from the bladder to the upper urinary tract and is distinguished in primary and secondary. It is present in 25-70
of children who have a urinary tract infection (UTI) associated with pyelonephritis, the association between UTI and VUR predisposes children to have renal scarring with consequent alteration of the functionality until chronic renal failure. MATERIAL AND METHODS: We realized a review of the literature on the endoscopic treatment of vesico-ureteral reflux analyzing the different techniques, materials used for endoscopic injection, indications and complications described in the literature. RESULTS: Over 100 articles we found on the endoscopic treatment of reflux with indications, complications and outcomes in the short, medium and long term. Of these we selected the most recent and current European and American Guidelines. CONCLUSIONS: Endoscopic treatment of reflux has become gradually the technique of choice for the primary treatment of vesico-ureteral reflux associated with pyelonephritis or urinary tract infections and permits to delay the use of open surgery.