Αρχειοθήκη ιστολογίου

Κυριακή 5 Νοεμβρίου 2017

Pediatric acute mastoiditis in the era of pneumococcal vaccination

Objectives/Hypothesis

The objective was to describe trends in the annual prevalence of hospitalization for pediatric acute mastoiditis since introduction of the 7-valent pneumococcal vaccine in 2000 and the 13-valent vaccine in 2010.

Study Design

Cross-sectional retrospective data analysis.

Methods

The Kids' Inpatient Database from years 2000 to 2012 was analyzed. To determine the annual prevalence of hospitalization for acute mastoiditis, nationally weighted frequencies of hospitalization for children <21 years with acute mastoiditis diagnoses were collected. Trend analysis of hospitalization rates from 2000 to -2012 was performed.

Results

From 2000 to 2012, there was no significant trend in hospitalization rates for acute mastoiditis overall (1.38 and 1.43 per 100,000 persons in 2000 and 2012, respectively; P = .86) or by age group. When comparing hospitalization rates at time points 2000 and 2012, children <1 year (4.65 and 3.27 per 100,000 persons, P = .0023) and 1 to 2 years of age (3.95 and 3.18 per 100,000 persons, respectively; P = .0107) demonstrated declines in hospitalization over time. Between 2009 and 2012, hospitalization rates also significantly declined for children aged <1 year (4.50 to 3.27 per 100,000 persons, P = .0056) and 1 to 2 years (4.30 to 3.18 per 100,000 persons, P = .0002) but increased for children 5 to 9 years (1.10 to 1.81 per 100,000 persons, P < .0001) and 10 to 20 years of age (0.41 to 0.72 per 100,000 persons, P < .0001).

Conclusions

Despite introduction of two pneumococcal vaccines, rates of hospitalization for pediatric acute mastoiditis did not decline between 2000 and 2012. Between 2009 and 2012, however, children 0 to 2 years of age showed declining hospitalization rates, possibly reflecting the protective benefit of the 13-valent pneumococcal vaccine.

Level of Evidence

4 Laryngoscope, 2017



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Current practices for voice rest recommendations after phonomicrosurgery

Objectives/Hypothesis

The aim of this study was to understand current protocols for voice rest implemented by laryngologists immediately after phonomicrosurgery for benign vocal fold lesions.

Study Design

Cross-sectional survey.

Methods

A 24-item survey was sent via electronic mail to laryngologists across the country to gather data on their recommendations of type and dosage of voice rest, factors involved in this decision, and recommendations for other behavioral modifications.

Results

A majority of the laryngologists implement 7 days of complete voice rest for nodules, cysts, polyps, and Reinke's edema, 1 to 4 days for leukoplakia and papilloma, and over 8 days of relative voice rest for most lesions. A majority of the laryngologists also employ a combination of complete and relative voice rest.

Conclusions

The more common recommendation for complete voice rest is 7 days for nodules, cysts, polyps, and Reinke's edema, and 1 to 4 days for leukoplakia and papilloma. Relative voice rest when recommended is typically recommended for over 8 days. Voice rest recommendations were not affected by surgery type alone, but were determined by either lesion type alone or lesion type combined with surgery type.

Levels of Evidence

4. Laryngoscope, 2017



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Prediction of mortality and morbidity in head and neck cancer patients 80 years of age and older undergoing surgery

Objectives

To determine postoperative complications and mortality rates in octogenarian and older head and neck cancer patients undergoing ablative surgical resections and to identify factors associated with postoperative morbidity and mortality.

Methods

Retrospective cohort study investigating risk factors for 30-day serious complication risk and 90-day mortality risk for patients aged 80 years and older who underwent ablative head and neck oncologic surgical procedures at an academic tertiary care center between 2005 and 2015.

Results

Of the 219 patients who underwent 241 surgeries, 74 patients experienced serious complications within 30 days and 25 died within 90 days of surgery. American Society of Anesthesiologists (ASA) score of 4 or greater, and operating room (OR) time ≥6 hours were independently associated with serious complications, whereas age ≥90 years, overall severe comorbidity score, presence of preoperative dysphagia, and large extent of resection were associated with increased risk of death in 90 days. Models to predict risk of 30-day serious complications and 90-day mortality were then developed.

Conclusion

Patient and surgical treatment factors predict risk of serious complications and mortality in patients aged 80 years and older undergoing ablative head and neck surgery. Predictive models may guide preoperative discussion with patients.

Level of Evidence

2b. Laryngoscope, 2017



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Vibratory function and healing outcomes after small intestinal submucosa biomaterial implantation for chronic vocal fold scar

Objectives/Hypothesis

Vocal fold scar is a major cause of dysphonia, and optimal treatments do not currently exist. Small intestinal submucosa (SIS) is a biomaterial developed for the treatment of a variety of pathologies. The purpose of this study was to investigate the effects of SIS implantation on tissue remodeling in scarred vocal folds using routine staining, immunohistochemistry, and high-speed videoendoscopy (HSV).

Study Design

Prospective, blinded group analysis.

Methods

Thirteen New Zealand White rabbits underwent a vocal fold scarring procedure followed by microflap elevation with or without SIS implantation. Seven months later, they underwent a phonation procedure with HSV and laryngeal harvest. Alcian blue and elastica van Gieson staining and immunohistochemistry for collagen types I and III were used to evaluate histological healing outcomes. Dynamic functional remodeling of the scarred vocal fold in the presence of SIS implants was evaluated using HSV imaging to capture restoration of vibratory amplitude, amplitude ratio, and left-right phase symmetry.

Results

Density of collagen I was significantly decreased in SIS versus microflap-treated vocal folds. No differences were found between groups for hyaluronic acid, elastin, or collagen type III. Organization of elastin in the subepithelial region appeared to affect amplitude of vibration and the shape of the vocal fold edge.

Conclusions

SIS implantation into chronic scar reduced the density of collagen I deposits. There was no evidence of a negative impact or complication from SIS implantation. Regardless of treatment type, organization of elastin in the subepithelial region may be important to vibratory outcomes.

Level of Evidence

NA Laryngoscope, 2017



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Is multidisciplinary team care for head and neck cancer worth it?



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Clinical trials in rhinosinusitis: Identifying areas for improvement

Objectives/Hypothesis

To characterize trends in rhinosinusitis clinical trials to provide recommendations for therapeutic directions, highlight possible redundancy, and provide a framework for prioritization of future clinical trials.

Study Design

Database analysis.

Methods

Data were collected from ClinicalTrials.gov including all clinical trials that focused on rhinosinusitis with the exclusion of trials withdrawn prior to enrollment. Variables recorded included study design, study population, pharmaceutical involvement, publication, and whether a trial was a medical or surgical intervention. Associated publications were identified using the PubMed, Embase, and Cochrane databases.

Results

There were 269 rhinosinusitis clinical trials, dating from 1993 to 2017, that met inclusion reauirements. Of the studies included in this analysis, 51.7% had at least one scientific publication, and of those with publications, 80.6% had positive results and 19.3% had negative results. Twenty-three clinical trials (8.5%) studied drugs already approved for rhinosinusitis, 113 (42.0%) trials studied drugs that were approved for other uses, 42 (15.6%) trials studied experimental drugs, and 102 (39.4%) studied surgical intervention. Of the trials studying drugs, the data showed many clinical trials that studied the same drug. The data demonstrate a steady decline in clinical trials with medical intervention and a rise in clinical trials with surgical intervention.

Conclusions

This analysis is the first to characterize rhinosinusitis clinical trials, highlighting the over-representation of certain drugs and demonstrating an increased focus on clinical trials employing surgical intervention. We provide a framework to discuss prioritization of future studies to guide clinical and research practice.

Level of Evidence

4. Laryngoscope, 2017



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The relationship between endolymphatic hydrops in the vestibule and low-frequency air-bone gaps

Objectives/Hypothesis

To investigate the relationship between endolymphatic hydrops and hearing level, focusing on significant vestibular endolymphatic hydrops adjacent to the stapes footplate and low-frequency air-bone gaps.

Study Design

Retrospective study.

Methods

The study included 1,548 ears from 775 patients who underwent magnetic resonance imaging examination in our university hospital to investigate possible endolymphatic hydrops between January 2012 and December 2015. Ears were evaluated by magnetic resonance imaging performed 4 hours after intravenous injection of a standard dose of gadodiamide hydrate and/or 24 hours after intratympanic injection of gadopentetate dimeglumine diluted eightfold. Comparison of hearing thresholds on pure-tone audiometry was performed between ears having endolymphatic hydrops adjacent to the stapes footplate and those having nonadjacent endolymphatic hydrops.

Results

Forty-one ears (22 men and 19 women, mean age 48.4 years) showed significant cochlear and vestibular endolymphatic hydrops adjacent to the stapes footplate, and 79 ears (30 men and 49 women, mean age 45.0 years) showed significant nonadjacent cochlear and vestibular endolymphatic hydrops. The average air-bone gap at 250 Hz was significantly higher in the group of ears with adjacent hydrops than in those with nonadjacent hydrops.

Conclusions

The appearance of low-frequency air-bone gaps suggests deterioration of endolymphatic hydrops, particularly in ears with Ménière's disease, and could be a useful indicator for evaluating and treating patients with endolymphatic hydrops.

Level of Evidence

4. Laryngoscope, 2017



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Motor and sensory morbidity associated with the anterolateral thigh perforator free flap

Objective

To quantify changes in motor function, sensation, and lower extremity quality of life following anterior lateral thigh free flap (ALT) resection.

Methods

This mixed methods study contained both a prospective cohort arm (n = 20) and retrospective cross-sectional arm (n = 20). In both arms, patients underwent formal motor and sensation testing of the ipsilateral and contralateral thigh by sphygmomanometry and monofilament testing. In the prospective arm, data was collected preoperatively and at the 6-month and 1-year follow-up visits. In the retrospective arm, consecutive patients with a minimum of 6-month postoperative follow-up were enrolled.

Results

Postoperatively, 82% of participants endorsed some degree of numbness and tingling at the donor site. On monofilament testing, patients from the prospective arm showed decreased sensibility of the midthigh at both the 6- and 12-month assessment (P < 0.01). Two-point discrimination scores were moderately correlated with the cross-sectional surface area of the flap. Donor thighs demonstrated a similar peak isometric quadriceps contraction (retrospective [retro]: 47 ± 24 mmHg, prospective [pro]: 90 ± 36 mmHg) to the unoperated thighs (retro: 43 mmHg ± 22, pro: 69 ± 35.3 mmHg, P = 0.49). When stratified by perforator anatomy, no significant differences were noted. Subjective donor site morbidity measured with the lower extremity function scale demonstrated no statistically significant difference between the preoperative and 12-month postoperative assessment.

Conclusion

The ALT flap offers minimal donor site morbidity. Reduced sensibility of the ALT flap is a common complaint among patients. Quadriceps strength is not significantly affected by an ALT free flap harvest.

Level of Evidence

4. Laryngoscope, 2017



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Pediatric tinnitus: A clinical perspective

Objectives/Hypothesis

To define the clinical features and natural history of pediatric tinnitus from a practicing otolaryngologist's perspective and formulate hypotheses therein.

Study Design

Retrospective chart review.

Methods

A retrospective chart review of the electronic medical record was undertaken. Only relevant records with a prior otolaryngology clinic visit and audiologic testing were included. Patients seen during the last 2 years of the study period were contacted and completed a questionnaire to assess change in tinnitus and quantify potential alterations in quality of life, associated symptoms, and natural history.

Results

One hundred eighty subjects with mean/median age of 11.5/11.5 years were identified. Hearing loss was identified in 40 subjects (22.2%). Etiology of tinnitus was identified in 95 subjects (52.8 %). Tinnitus-specific and/or nonspecific therapies were given to 80 subjects (44.4%). Of the 54 available subjects, 28 (51.9%) participated in the telephone questionnaire. Tinnitus complaints shifted favorably to the improvement or resolution categories (P = .001) between the initial clinic visit and the telephone interview. Shorter duration of tinnitus was associated with a higher probability of having improved tinnitus (P = .046).

Conclusions

This study distinguishes pediatric tinnitus from adult tinnitus in terms of lower association with underlying hearing loss, lower likelihood of reported anxiety, and higher likelihood of improvement and resolution. There are opportunities for tinnitus prevention in the areas of reducing head injury and noise-induced hearing loss.

Level of Evidence

4 Laryngoscope, 2017



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Trust and Justice in Big Data Analytics: Bringing the Philosophical Literature on Trust to Bear on the Ethics of Consent

Abstract

Much bioethical literature and policy guidances for big data analytics in biomedical research emphasize the importance of trust. It is essential that potential participants trust so they will allow their data to be used to further research. However, comparatively, little guidance is offered as to what trustworthy oversight mechanisms are, or how policy should support them, as data are collected, shared, and used. Generally, "trust" is not characterized well enough, or meaningfully enough, for the term to be systematically applied in policy development. Yet points made in the philosophical literature on trust can help. They allow us, not only to better distinguish the different ways the term "trust" may be interpreted, but also to better determine how different approaches to trust can align with policy and governance—in what ways they may relate to key bioethical concepts and related laws, and in what ways they can help to balance individual and group interests in data sharing. This article draws from the philosophical literature on trust to identify a relationship among consent, trust, and justice. Specifically, parallels are drawn between "character-trustworthiness" and "natural justice," a set of widely held legal safeguards intended to ensure decision-makers follow a pattern of procedural fairness which protects the rights of the individual and thereby maintains public confidence in the decision-making process. Relevance to traditional bioethical principles, established laws, and consent procedures are addressed throughout. In conclusion, policy actions are suggested.



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Scrotal calcinosis: two case reports

Scrotal calcinosis is a rare and benign condition. It usually gives rise to few symptoms, and the impact is mainly functional and aesthetic. It is considered part of dystrophic calcinosis cutis. Surgical manag...

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Downregulation of BDH2 modulates iron homeostasis and promotes DNA demethylation in CD4+ T cells of systemic lupus erythematosus

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Publication date: Available online 4 November 2017
Source:Clinical Immunology
Author(s): Ming Zhao, Meng-ying Li, Xiao-fei Gao, Su-jie Jia, Ke-qin Gao, Yin Zhou, Hui-hui Zhang, Yi Huang, Jing Wang, Hai-jing Wu, Qian-jin Lu
DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4+ T cells. Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4+ T cells compared with healthy controls. The decreased BDH2 contributed to DNA hyper-hydroxymethylation and hypomethylation via increasing intracellular iron in CD4+ T cells, which led to overexpression of immune related genes. Moreover, we showed that BDH2 was the target gene of miR-21. miR-21 promoted DNA demethylation in CD4+ T cells through inhibiting BDH2 expression. Our data demonstrated that the dysregulation of iron homeostasis in CD4+ T cells induced by BDH2 deficiency contributes to DNA demethylation and self-reactive T cells in SLE.



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Natural killer cells play an essential role in resolution of antigen-induced inflammation in mice

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Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Osk U.U. Anuforo, Stefania P. Bjarnarson, Hulda S. Jonasdottir, Martin Giera, Ingibjorg Hardardottir, Jona Freysdottir
This study examined whether NK cells are important for resolution of antigen-induced inflammation. C57BL/6 mice were immunized twice with methylated BSA (mBSA) and inflammation induced by intraperitoneal injection of mBSA. Mice were injected intravenously with anti-asialo GM1 (αASGM1) or a control antibody 24h prior to peritonitis induction and peritoneal exudate collected at different time points. Expression of surface molecules and apoptosis on peritoneal cells was determined by flow cytometry and concentration of chemokines, cytokines, soluble cytokine receptors and lipid mediators by ELISA and LC–MS/MS. Apoptosis in parathymic lymph nodes and spleens was determined by TUNEL staining. Mice administered αASGM1 had lower peritoneal NK cell numbers and a higher number of peritoneal neutrophils 12h after induction of inflammation than control mice. The number of neutrophils was still high in the αASGM1 treated mice when their number had returned to baseline levels in the control mice, 48h after induction of inflammation. Peritoneal concentrations of the neutrophil regulators G-CSF and IL-12p40 were higher at 12h in the αASGM1 treated mice than in the control mice, whereas concentrations of lipid mediators implicated in resolution of inflammation, i.e. LXA4 and PGE2, were lower. Reduced apoptosis was detected in peritoneal neutrophils as well as in draining lymph nodes and spleens from the αASGM1 treated mice compared with that in the control mice. In addition, αASGM1 treated mice had lower number of peritoneal NK cells expressing NKp46 and NKG2D, receptors implicated in NK cell-induced neutrophil apoptosis. Furthermore, αASGM1 treatment completely blocked the increase in CD27+ NK cells that occurred in control mice following induction of inflammation, but CD27+ NK cells have been suggested to have a regulatory role. These results indicate a crucial role for NK cells in resolution of antigen-induced inflammation and suggest their importance in tempering neutrophil recruitment and maintaining neutrophil apoptosis.



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Traitement du lupus érythémateux par le bélimumab en pratique courante : étude rétrospective de 15 malades

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Publication date: Available online 4 November 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): E. Garval, J.-L. Pennaforte, R. Jaussaud, A. Servettaz, P. Bernard, Z. Reguiai
IntroductionLe bélimumab (anticorps monoclonal anti-BLyS) a été récemment commercialisé dans le traitement du lupus érythémateux (LE) systémique. Le but de cette étude était d'en décrire l'efficacité, la tolérance, l'impact sur les paramètres sérologiques du LE et le rôle d'épargne des traitements de fond en pratique courante.Malades et méthodesCette étude rétrospective menée au CHU de Reims incluait tous les malades atteints de LE traités par bélimumab entre 2012 et 2016. L'efficacité du traitement était évaluée sur l'évolution clinique, la normalisation des concentrations d'anticorps anti-DNA et de complément, et l'épargne des autres traitements du LE.RésultatsUne réponse thérapeutique était obtenue chez 9 des 15 malades inclus (60 %), à type de rémission partielle pour 8 d'entre eux. La concentration médiane d'anti-DNA était de 50UI/mL (4 à 50) et celle de C3 sérique de 0,82g/L (0,36 à 1,23) à l'instauration du bélimumab, versus respectivement 25,5UI/mL (2 à 50) et 0,89g/L (0,34 à 1,22) à la date des dernières nouvelles (DDN), sans modification significative (respectivement p=0,12 et p=0,45). La posologie médiane de prednisone à l'instauration du bélimumab passait de 9,5mg/j (0 à 18) à 6mg/j (0 à 20) à la DDN. Huit malades (53 %) ont présenté des effets secondaires, toujours minimes.ConclusionLe bélimumab a eu chez 15 malades une efficacité modérée et une faible toxicité ; il a permis une épargne cortisonique modérée, en vue de limiter les effets secondaires de la corticothérapie au long cours.BackgroundBelimumab (an anti-BLyS monoclonal antibody) was recently approved for the treatment of systemic lupus erythematosus (SLE). The aim of the study was to describe efficacy and safety of the drug as well as its impact on serologic parameters and the role of long-term systemic sparing of treatment in clinical practice in LE.Patients and methodsWe conducted a retrospective study at Reims University Hospital between 2012 and 2016 including consecutive patients with LE treated with belimumab. Efficacy was evaluated in terms of clinical progression, and normalisation of laboratory factors (anti-DNA antibody and C3 serum levels) and sparing of associated long-term systemic therapies for LE.ResultsAmong the 15 patients included, a therapeutic response was obtained in 9 patients (60%), with partial remission in 8 of 9 cases. The median titre of anti-DNA antibody was 50IU/mL (range: 4–50) and the median C3 level was 0.82g/L (range: 0.36–1.23) before initiation of belimumab, vs. 25.5IU/mL (range: 2–50) and 0.89g/L (range: 0.34–1.22) at the last evaluation, respectively, without significant modification (P=0.12 and P=0.45). The median dose of prednisone at the time of the first belimumab infusion was reduced from 9.5mg/day (range: 0–18) to 6mg/day (range: 0–20) at the last clinical evaluation. Eight patients (53%) experienced adverse events, and these were very slight or moderate in all cases.ConclusionBelimumab appears to be an effective and well-tolerated treatment for moderately severe systemic LE, allowing sparing of maintenance corticosteroid therapy in order to decrease its frequent adverse events.



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Human plasma C3 is essential for the development of memory B, but not T, lymphocytes

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Publication date: Available online 4 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Anaïs Jiménez-Reinoso, Ana V. Marin, Marta Subias, Alberto López-Lera, Elena Román-Ortiz, Kathryn Payne, Cindy S. Ma, Giuseppina Arbore, Martin Kolev, Simon J. Freeley, Claudia Kemper, Stuart G. Tangye, Edgar Fernández-Malavé, Santiago Rodríguez de Córdoba, Margarita López-Trascasa, José R. Regueiro

Teaser

Primary or secondary plasma C3 deficiency due to mutations in C3 or in complement Factor I impairs memory B, but not T, cell differentiation, but does not preclude intracellular C3 fragment expression in lymphocytes.


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TRIM21 negatively regulates intestinal mucosal inflammation through inhibiting Th1/Th17 cell differentiation in inflammatory bowel diseases

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Publication date: Available online 4 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Guangxi Zhou, Wei Wu, Lin Yu, Tianming Yu, Wenjing Yang, Ping Wang, Xiaoping Zhang, Yingzi Cong, Zhanju Liu
BackgroundTripartite motif-containing (TRIM)21 has been implicated in pathogenesis of several types of autoimmune diseases.ObjectiveWe sought to elucidate expression of TRIM21 in patients with inflammatory bowel disease (IBD) and its role in regulating intestinal mucosal inflammation.MethodsTRIM21 expression was analyzed in inflamed mucosa of IBD patients by qRT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were transfected with lentivirus-expressing-TRIM21 (LV-TRIM21) or LV-sh-TRIM21, and cytokine expression was determined by qRT-PCR and ELISA. TRIM21−/− mice were generated, and trinitrobenzene sulphonic acid (TNBS)- and CD45RBhighCD4+ T cell-induced colitis models were established to determine its role in the induction of intestinal inflammation.ResultsTRIM21 was predominantly expressed in CD4+ T cells and markedly decreased in inflamed mucosa of IBD patients compared with healthy controls. Ectopic expression of TRIM21 inhibited IBD CD4+ T cells to differentiate into T helper (Th)1 and Th17 cells, whereas downregulation of TRIM21 had opposite effects. TRIM21−/− mice developed more severe colitis following administration of TNBS compared with wild-type mice, characterized by increased expression of IFN-γ, TNF-α, and IL-17A in the colon. TRIM21−/− CD45RBhighCD4+ T cells reconstituted into Rag-1−/− mice induced more severe colitis than wild-type controls. Mechanistically, IRF3 was identified as a functional downstream target of TRIM21, in that silencing of IRF3 suppressed TRIM21−/−CD4+ T cell differentiation into Th1 and Th17 cells.ConclusionsTRIM21 plays a protective role in mucosal inflammation through inhibiting Th1 and Th17 cell differentiation. Thus, TRIM21 may serve as a potential therapeutic target for treatment of IBD.

Teaser

●TRIM21 is decreased in inflamed mucosa of patients with active IBD and plays a protective role in mucosal inflammation through inhibiting Th1 and Th17 cell differentiation. TRIM21 may serve as a potential therapeutic target for treatment of IBD.


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