TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which decreases in contact hypersensitivity

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Keng Wang, Lei Tao, Jianbing Su, Yueyang Zhang, Binhua Zou, Yiyuan Wang, Min Zou, Nana Chen, Linsheng Lei, Xiaojuan Li
Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5⁺CD1d^hi Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5⁺CD1d^hi Bregs. In this study, we isolated splenocytes or splenic CD19⁺ B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5⁺CD1d^hi Bregs by flow cytometry. FasL expression in CD5⁺CD1d^hi B cells was rapidly increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40 combinations failed to stimulate FasL expression in CD5⁺CD1d^hi B cells although the IL-10 production was up-regulated in this subset. In addition, LPS and other B10-cell inducers increased the expression of surface molecules like CD86 and CD25, which are correlated to the regulatory functions of B cells. Furthermore, NF-κB and NF-AT inhibitors decreased the TLR4-activated FasL expression in CD5⁺CD1d^hi B cells. Then we sorted splenic CD5⁺CD1d^hi Bregs using flow cytometry and found that TLR4-activated CD5⁺CD1d^hi Bregs suppressed the proliferation of CFSE-labeled CD4⁺ T cells in vitro, which was partly blocked by anti-FasL antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL expression in splenic CD5⁺CD1d^hi B cells was decreased compared to the control group after TLR4 ligation. Our findings suggest that the regulatory function of CD5⁺CD1d^hi B cells could be partly mediated by Fas-FasL pathway and this FasL expressing CD5⁺CD1d^hi Bregs might participate in the regulation of inflammatory diseases.



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RhoB induces the production of proinflammatory cytokines in TLR-triggered macrophages

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Shuyuan Liu, Lisong Huang, Zhusen Lin, Yuanqin Hu, Ruifeng Chen, Liqiu Wang, Yi Shan
Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular patterns on microorganisms, thus acting as important components of innate immunity against invading pathogens. Many positive and negative regulators of TLR-triggered signaling have been identified. The Rho GTPase RhoB plays a key role in cell migration, division and polarity; however, the function and regulatory mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be investigated. Here, we report that the expression of RhoB is induced by TLR agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages. Knockdown of RhoB expression markedly decreased TLR ligand-induced activation of mitogen activated protein kinases and nuclear factor-κB (NF-κB), and the production of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β in macrophages stimulated with TLR ligands. Furthermore, we demonstrated that RhoB interacts with major histocompatibility complex class II (MHCII) α chain, but not β chain, in endosomes of macrophages. Knockdown of MHCII expression greatly reduced the interaction of RhoB with Btk, and attenuated the induction of NF-κB and interferon β activity by RhoB upon LPS stimulation. These findings suggest that RhoB is a positive physiological regulator of TLRs signaling via binding to MHCII in macrophages, and therefore RhoB may be a potential therapeutic target in inflammatory diseases.



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Clasificación de las resecciones transorales en la orofaringe: propuesta del grupo de trabajo de la Sociedad Catalana de Otorrinolaringología

Publication date: Available online 12 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): David Virós Porcuna, Francisco Avilés Jurado, Carlos Pollán Guisasola, Rosa Delia Ramírez Ruiz, Jacinto García Lorenzo, Marc Tobed Secall, Isabel Vilaseca González, José Miguel Costa González, Josep Soteras Olle, Francesc Casamitjana Claramunt, Anna Sumarroca Trouboul, Rafael Hijano Esqué, Guillem Viscasillas Pallàs, Manel Mañós Pujol, Miquel Quer Agustí
Introducción y objetivosLa cirugía mínimamente invasiva ha presentado una expansión muy importante en la última década. Con el objetivo de aportar un lenguaje común tras cirugía transoral de la orofaringe, se ha creado un sistema de clasificación de las resecciones en esta zona, independientemente de la instrumentalización utilizada.MétodosDesde el Grupo de Trabajo en Oncología de la Sociedad Catalana de Otorrinolaringología, se presenta una propuesta de clasificación basada en una división topográfica de las diferentes zonas de la orofaringe, así como en la afectación de las estructuras anexas según las vías anatómicas de extensión de estos tumores.ResultadosLa clasificación se inicia utilizando la letra D o I según la lateralidad sea derecha (D) o izquierda (I). A continuación se coloca el número del área resecada. Esta numeración define las zonas iniciando a nivel craneal donde el área I sería el paladar blando, el área II lateral en la zona amigdalina, el área III en la base de lengua, el área IV en los repliegues glosoepiglóticos, la epiglotis y repliegues faringoepiglóticos, el área V pared orofaríngea posterior y VI el trígono retromolar.Se añade el sufijo p si la resección afecta profundamente al plano submucoso de la zona comprometida. Las diferentes áreas propuestas tendrían, de una forma teórica, diferentes implicaciones funcionales.ConclusionesPropuesta de sistema de clasificación por áreas que permite definir diferentes tipos de cirugía transoral de la orofaringe así como compartir los resultados y ayudar en la docencia de este tipo de técnicas.Introduction and goalsThere has been a very significant increase in the use of minimally invasive surgery has in the last decade. In order to provide a common language after transoral surgery of the oropharynx, a system for classifying resections has been created in this area, regardless of the instrumentation used.MethodsFrom the Oncology Working Group of the Catalan Society of Otorhinolaryngology, a proposal for classification based on a topographical division of the different areas of the oropharynx is presented, as also based on the invasion of the related structures according to the anatomical routes of extension of these tumours.ResultsThe classification starts using the letter D or I according to laterality either right (D) or left (I). The number of the resected area is then placed. This numbering defines the zones beginning at the cranial level where area I would be the soft palate, lateral area II in the tonsillar area, area III in the tongue base, area IV in the glossoepiglottic folds, epiglottis and pharyngoepiglottic folds, area V posterior oropharyngeal wall and VI the retromolar trigone.The suffix p is added if the resection deeply affects the submucosal plane of the compromised area. The different proposed areas would, in theory, have different functional implications.ConclusionsProposal for a system of classification by area to definedifferent types of transoral surgery of the oropharynx, and enable as sharing of results and helps in teaching this type of technique.



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Aprendiendo de la demanda asistencial en el síndrome de apnea del sueño infantil

Publication date: Available online 12 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): Paz Martinez-Beneyto, Cristina E. Soria Checa, Paloma Botella-Rocamora, Inés Rincon-Piedrahita, Francisco J. Garcia Callejo, Jaime Marco Algarra
Introducción y objetivosEl síndrome de apnea-hipopnea del sueño (SAHS) pediátrico engloba alteraciones multisistémicas que afectan al estado general de salud, valorado indirectamente mediante el estudio de la demanda asistencial. Objetivo: cuantificar la frecuentación de consultas médicas en niños con SAHS durante 5 años y compararla con una población sana.MétodosEstudio casos-control longitudinal ambispectivo en un hospital del sistema nacional de salud. Reclutamos a 69 niños remitidos por SAHS sin otras patologías para que la demanda asistencial fuera predominantemente atribuida al SAHS. Se seleccionó a otros 69 niños sanos como grupo control. Obtuvimos datos de frecuentación durante 5 años: el año en el que se realizó el tratamiento del SAHS («año 0»), 1 y 2 años antes («año –1» y «año –2»), y 1 y 2 años tras el tratamiento («año+1» y «año+2»).ResultadosEl índice de frecuentación (IF), descrito como cociente entre demanda asistencial por los niños con SAHS y niños sanos, fue 1,89 durante el año –2 y 2,15 durante el año –1 (p<0,05). El tratamiento disminuyó la utilización, con IF de 1,59 durante el año+1 y 1,72 en el año+2 (p<0,05). Las principales causas de sobrefrecuentación fueron otorrinolaringológicas y neumológicas.ConclusionesLos niños con SAHS muestran mayor demanda asistencial, al menos 2 años antes del tratamiento, lo que implica un deterioro de la salud global que pudiera estar presente años antes de que la abordemos. El tratamiento repercute en una mejora, aunque permanece alta tras el tratamiento, sugiriendo enfermedad residual o secuelas.Introduction and objectivesPaediatric Obstructive Sleep Apnoea-Hypopnoea Syndrome (OSAS) is a multisystemic condition affecting child's health status that may be investigated analyzing demand for healthcare. Objective: to quantify the frequency of medical consultations in children with OSAS over a 5-year period, compared to a healthy population.MethodsA longitudinal, case-control, ambispective study was conducted at a hospital pertaining to the national public health system. 69 consecutive children referred for OSAS were recruited with no diseases other than OSAS so that healthcare demand was purely attributed to this condition. Matched healthy control children were selected to compare these data. Data regarding frequency of the medical consultations were obtained over 5 years: the year of the treatment ("Year0"), 1 and 2 years before ("Year -1" and "Year -2" respectively), and 1 and 2 years after treatment ("Year+1" and "Year+2")ResultsFrequentation Index (FI), as ratio between the use of health services by OSAS children and healthy controls was 1.89 during Year-2, and 2.15 during Year-1 (P<.05). Treatment diminishes utilization, with FI of 159 during year+1 and 1.72 during year+2 (P<.05). The main causes of attendance were otolaryngological and pneumological diseases, improving after treatment.ConclusionsChildren suffering from OSAS demand more healthcare services, at least 2 years before treatment, implying that the disease could be present years before we manage it. Therapeutic actions improve healthcare services utilization, although remain higher than for controls, which suggests OSAS sequelae or residual disease.



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Comentarios sobre el hallazgo de nervio laríngeo derecho no recurrente durante la tiroidectomía

Publication date: Available online 12 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): José Luis Pardal-Refoyo




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Discrepancy between clinical and pathological neck staging in oral cavity carcinomas

Publication date: Available online 12 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): Vânia Henriques, Eduardo Breda, Eurico Monteiro
IntroductionThe presence of cervical lymph node metastases in patients with oral cavity squamous cell carcinoma reduces survival by up to 50%.ObjectiveThe aims of this study are to assess the accuracy of clinical N staging versus pathological N staging and its impact on survival in order to identify predictive factors associated with the presence of occult neck metastases.MethodsOutcomes of 105 patients with oral cavity squamous cell carcinoma who underwent surgical treatment of the primary tumor and neck were retrospectively evaluated.ResultsFor pN0 and pN+ patients 5-year overall survival was respectively 53% and 27%; disease specific survival was 66% for pN0 and 33% for pN+. Patients with clinical negative lymph nodes were pathologically upstaged in 62% of cases. Disease specific survival according to staging discrepancy had statistically significant impact on survival (p=0.009).ConclusionClinical staging usually underestimates the presence of nodal disease. Neck dissection should be performed in cN0 oral cavity squamous cell carcinoma.



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Síndrome de Alagille: hipoplasia de canales semicirculares posteriores

Publication date: Available online 12 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): Alexandre Perez-Girbes, Miguel Mazón, Elena Pont




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