References of "Louis, Renaud"
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See detailNovel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
EL SHAZLY, Amr ULg; Begon, Dominique ULg; KUSTERMANS, Gaëlle ULg et al

in Journal of Biological Chemistry (2013), 288(2), 1374-84

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]

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See detailLung function and airway inflammation monitoring after hematopoietic stem cell transplantation.
Moermans, Catherine ULg; Poulet, Christophe ULg; HENKET, Monique ULg et al

in Respiratory Medicine (2013), 107

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the ... [more ▼]

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. Results For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38–79)} compared to healthy subjects matched for age {Median (IQR): 49% (17–67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. Conclusions There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year. [less ▲]

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See detailDistribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation.
SCHLEICH, FLorence ULg; Manise, Maïté ULg; Sele, Jocelyne et al

in BMC Pulmonary Medicine (2013), 13(1), 11

ABSTRACT: BACKGROUND: Phenotyping asthma according to airway inflammation allows identification of responders to targeted therapy. Induced sputum is technically demanding. We aimed to identify predictors ... [more ▼]

ABSTRACT: BACKGROUND: Phenotyping asthma according to airway inflammation allows identification of responders to targeted therapy. Induced sputum is technically demanding. We aimed to identify predictors of sputum inflammatory phenotypes according to easily available clinical characteristics. METHODS: This retrospective study was conducted in 508 asthmatics with successful sputum induction recruited from the University Asthma Clinic of Liege. Receiver-operating characteristic (ROC) curve and multiple logistic regression analysis were used to assess the relationship between sputum eosinophil or neutrophil count and a set of covariates. Equations predicting sputum eosinophils and neutrophils were then validated in an independent group of asthmatics. RESULTS: Eosinophilic (>=3%) and neutrophilic (>=76%) airway inflammation were observed in 46% and 18% of patients respectively. Predictors of sputum eosinophilia >=3% were high blood eosinophils, FENO and IgE level and low FEV1/FVC. The derived equation was validated with a Cohen's kappa coefficient of 0.59 (p < 0.0001). ROC curves showed a cut-off value of 220/mm3 (AUC = 0.79, p < 0.0001) or 3% (AUC = 0.81, p < 0.0001) for blood eosinophils to identify sputum eosinophilia >=3%. Independent predictors of sputum neutrophilia were advanced age and high FRC but not blood neutrophil count. CONCLUSION: Eosinophilic and paucigranulocytic asthma are the dominant inflammatory phenotypes. Blood eosinophils provide a practical alternative to predict sputum eosinophilia but sputum neutrophil count is poorly related to blood neutrophils. [less ▲]

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See detailSputum IgE and Cytokines in Asthma: Relationship with Sputum Cellular Profile.
Manise, Maïté ULg; Holtappels, Gabriele; Van Crombruggen, Koen et al

in PLoS ONE (2013), 8(3), 58388

BACKGROUND: Local IgE production may play a role in asthma pathogenesis. The aim of the study was to assess sputum total IgE and cytokines in asthmatics according to sputum cellular phenotype. METHODS: We ... [more ▼]

BACKGROUND: Local IgE production may play a role in asthma pathogenesis. The aim of the study was to assess sputum total IgE and cytokines in asthmatics according to sputum cellular phenotype. METHODS: We studied 122 subjects including 22 non atopic healthy subjects, 41 eosinophilic (sputum eosinophils >/=3%), 16 neutrophilic (sputum neutrophils >76%) and 43 pauci-granulocytic asthmatics (sputum eosinophils <3% and sputum neutrophils </=76%) recruited from the asthma clinic at CHU Liege. Sputum supernatant total IgE (tIgE) was measured by ImmunoCAP and sputum supernatant cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-gamma and TNF-alpha) were measured with the Luminex xMAP Technology by using commercially available Fluorokine MAP kits. RESULTS: After concentrating sputum samples, total IgE was detectable in the majority of subjects. Sputum IgE was raised in asthmatics when compared to healthy subjects. Overall, asthmatics did not significantly differ from healthy subjects with respect to cytokine levels. The eosinophilic asthma phenotype, however, was characterised by raised sputum tIgE, IL-5 and IL-13 compared to healthy subjects (p<0.001, p<0.001 and p<0.05 respectively) and pauci-granulocytic asthma (p<0.01, p<0.001 and p<0.05 respectively) and raised IL-5 compared to neutrophilic asthma (p<0.01). When patients were classified according to sputum IgE levels, it appeared that IL-5, IL-6, IL-17 and TNF-alpha sputum supernatant levels were raised in the "IgE high" asthmatics (IgE >/=0.1 kU/l) when compared to "IgE low" asthmatics (IgE<0.1 kU/l). CONCLUSION: The eosinophilic asthma phenotype was associated with raised sputum IgE and a Th2 cytokine profile. Raised sputum IgE was associated with a heterogeneous cytokine overproduction. [less ▲]

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See detailIncreased glutaredoxin-1 and decreased protein S-glutathionylation in sputum of asthmatics.
Kuipers, Ine; LOUIS, Renaud ULg; Manise, Maïté ULg et al

in The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology (2013), 41(2), 469-72

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See detailSpontaneous pneumomediastinum caused by bleomycin-induced pneumonitis
FRUSCH, Nicolas ULg; SERVAIS, Sophie ULg; DE PRIJCK, Bernard ULg et al

in Acta Clinica Belgica (2012)

We report the case of a 24-yr-old woman treated for lymphoma who developed bleomycin-induced intersitial pneumonia. This interstitial pneumonia was complicated by spontaneous pneumomediastinum ... [more ▼]

We report the case of a 24-yr-old woman treated for lymphoma who developed bleomycin-induced intersitial pneumonia. This interstitial pneumonia was complicated by spontaneous pneumomediastinum. Pneumomediastinum is an unfrequent side effect of high dose bleomycin-induced pneumonitis (BIP) and we describe the first case occurring with low-dose of bleomycin. [less ▲]

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See detailIs FE(NO50) useful diagnostic tool in suspected asthma?
SCHLEICH, FLorence ULg; ASANDEI, Raluca ULg; Manise, Maïté ULg et al

in International Journal of Clinical Practice (2012), 66(2), 158-65

Background: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of ... [more ▼]

Background: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of 50 ml/s (FE(NO50) ) remains a controversial diagnostic tool. Aim: To assess the ability of FE(NO50) to identify bronchial hyperresponsiveness (BHR) to methacholine (provocative concentration of methacholine causing a 20% fall in FEV(1) ; PC20M </= 16 mg/ml) and to establish whether or not symptoms relate to FE(NO50) and PC20M in patients with no demonstrated reversibility to beta(2) -agonist. Methods: We conducted a prospective study on 174 steroid naive patients with respiratory symptoms, forced expiratory volume in 1 s (FEV(1) ) >/= 70% predicted and no demonstrated reversibility to beta(2) -agonist. Patients answered to a standardised symptom questionnaire and underwent FE(NO50) and methacholine challenge. Receiver-operating characteristic (ROC) curve and logistic regression analysis assessed the relationship between PC20M and FE(NO50) , taking into account covariates (smoking, atopy, age, gender and FEV(1) ). Results: A total of 82 patients had a PC20M </= 16 mg/ml and had significantly higher FE(NO50) (19 ppb vs. 15 ppb; p < 0.05). By constructing ROC curve, we found that FE(NO50) cut-off value of 34 ppb was able to identify not only BHR with high specificity (95%) and positive predictive value (88%) but low sensitivity (35%) and negative predictive value (62%). When combining all variables into the logistic model, FE(NO50) (p = 0.0011) and FEV(1) (p < 0.0001) were independent predictors of BHR whereas age, gender, smoking and atopy had no influence. The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50) (p < 0.001 and p < 0.05, respectively). Conclusion: The value of FE(NO50) > 34 ppb has high predictive value of PC20M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated. However, FE(NO50) </= 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge. [less ▲]

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See detailShould we exclude elderly patients with chronic obstructive pulmonary disease from a long-time ambulatory pulmonary rehabilitation programme?
CORHAY, Jean-Louis ULg; NGUYEN DANG, Delphine ULg; DUYSINX, Bernard ULg et al

in Journal of Rehabilitation Medicine (2012), 44(5), 466-72

Objective: To assess the outcomes of a 6-month comprehensive multidisciplinary outpatient pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease according to age. Design ... [more ▼]

Objective: To assess the outcomes of a 6-month comprehensive multidisciplinary outpatient pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease according to age. Design: Prospective cohort study. Patients: A total of 140 patients with chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3-4) admitted to our centre for pulmonary rehabilitation. Methods: Patients were divided into 3 groups: group A (< 65 years), group B (65-74 years) and group C (>/= 75 years). All the patients received an education and individualized training programme. Pulmonary rehabilitation efficacy was evaluated at 6 months of treatment and 12 months post-treatment. Results: A total of 116 patients completed the pulmonary rehabilitation programme: 59 in group A (85.5%), 40 in group B (80%) and 17 in group C (80.9%). All the parameters studied (number of sessions, 6-min walking distance, isometric quadriceps strength, health-related quality of life, maximal load, peak oxygen uptake, maximal inspiratory and expiratory pressures) were significantly improved in each of the groups at 3 and 6 months compared with baseline. Moreover, percentage changes from baseline at 6 months for all of the parameters studied were not significantly different between age-groups. Conclusion: Pulmonary rehabilitation is efficient in elderly patients with severe and very severe chronic obstructive pulmonary disease, and their compliance with pulmonary rehabilitation was similar to that seen in younger groups. Therefore, elderly patients with chronic obstructive pulmonary disease should not be denied pulmonary rehabilitation. [less ▲]

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See detailCorticosteroids: still at the frontline in asthma treatment?
LOUIS, Renaud ULg; SCHLEICH, FLorence ULg; Barnes, Peter J.

in Clinics in Chest Medicine (2012), 33(3), 531-41

Inhaled corticosteroids (ICS) have led to improved asthma control and reduced asthma mortality in the Western world. ICS are effective in combating T-helper type 2-driven inflammation featuring mast cell ... [more ▼]

Inhaled corticosteroids (ICS) have led to improved asthma control and reduced asthma mortality in the Western world. ICS are effective in combating T-helper type 2-driven inflammation featuring mast cell and eosinophilic airway infiltration. Their effect on innate immunity-driven neutrophilic inflammation is poor and their ability to prevent airway remodeling and accelerated lung decline is controversial. Although ICS remain pivotal drugs in asthma management, research is needed to find drugs complementary to the combination ICS/long-acting beta2-agonist in refractory asthma and perhaps a new class of drugs as a first-line treatment in mild to moderate noneosinophilic asthma. [less ▲]

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See detailComment j'explore.... L'echographie thoracique: le nouveau stethoscope du pneumologue.
HEINEN, Vincent ULg; DUYSINX, Bernard ULg; CORHAY, Jean-Louis ULg et al

in Revue Médicale de Liège (2012), 67(10), 543-9

We now have access to a large library of publications validating transparietal thoracic echography in various clinical situations. Parietal lesions, including osteolysis, can be detected and biopsied ... [more ▼]

We now have access to a large library of publications validating transparietal thoracic echography in various clinical situations. Parietal lesions, including osteolysis, can be detected and biopsied during the thoracic ultrasound (TUS) examination. To evaluate the parietal extension of lung cancers, TUS has proved superior to tomodensitometry. Pleural effusions can be easily diagnosed and aspirated. Pneumothoraces can be detected using well defined lung artifacts with a high frequency probe. Pleural and peripheral lung nodules can be detected and biopsied with real time visualization; the procedure is safe and accurate. Lung consolidations with a pleural contact can be diagnosed; this is particularly useful for pregnant women. In conclusion, TUS is a precious diagnostic tool for chosen applications, and can help to guide interventional procedures. The portable devices are also very useful for bedridden patients or for out of hospital use. [less ▲]

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See detailLes traitements cibles dans l'asthme: confirmations, espoirs et deceptions.
SCHLEICH, FLorence ULg; LOUIS, Renaud ULg

in Revue Médicale de Liège (2012), 67 Spec No

Asthma is a chronic inflammatory disease of the airways. The inflammatory process is driven by different pathways involving cytokines and other protein mediators. Patients with severe asthma are at high ... [more ▼]

Asthma is a chronic inflammatory disease of the airways. The inflammatory process is driven by different pathways involving cytokines and other protein mediators. Patients with severe asthma are at high risk of severe exacerbations and death and have few therapeutic options available. Therefore, biological agents have been developed to help patients with refractory asthma by interfering with several compounds of the asthma inflammatory cascade. In addition to decreasing exacerbations, some of those treatments have a steroid sparing role and many beneficial effects in asthmatics. [less ▲]

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See detailL'asthme: une maladie complexe mettant en jeu facteurs environnementaux et terrain genetique.
LOUIS, Renaud ULg; SCHLEICH, FLorence ULg; Corhay, Jean-Louis ULg et al

in Revue Médicale de Liège (2012), 67(5-6), 286-91

Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have ... [more ▼]

Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype. [less ▲]

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See detailInduced sputum: not only for research but also for better patient management in asthma and COPD.
LOUIS, Renaud ULg

in Monaldi Archives for Chest Disease = Archivio Monaldi per le Malattie del Torace (2012), 77(1), 5-7

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See detailInterrelations genetique- environnement: la broncho-pneumopathie chronique obstructive.
Corhay, Jean-Louis ULg; Frusch, Nicolas; LOUIS, Renaud ULg

in Revue Médicale de Liège (2012), 67(5-6), 292-7

Smoking is the main environmental risk factor of COPD and accounts for 85% to 90% of COPD. However, 10-15% of COPD patients have never smoked and only a fraction of smokers ever develop COPD. Indeed ... [more ▼]

Smoking is the main environmental risk factor of COPD and accounts for 85% to 90% of COPD. However, 10-15% of COPD patients have never smoked and only a fraction of smokers ever develop COPD. Indeed, genetic and environmental (pollution, occupational and infectious) factors, also influence the risk of developing COPD. Finaly COPD must be considered as the clinical consequence of multiple complex interactions between environmental factors and genetic susceptibility. The latter is not clearly understood, with the exception of alpha-1 antitrypsin deficiency. In this article, we present the different aspects of this complex disease which is primarily environmental. [less ▲]

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See detailDisturbed Cytokine Production at the Systemic Level in Difficult-to-Control Atopic Asthma: Evidence for Raised Interleukin-4 and Decreased Interferon-gamma Release following Lipopolysaccharide Stimulation.
MANISE, Maïté ULg; SCHLEICH, FLorence ULg; QUAEDVLIEG, Valérie ULg et al

in International Archives of Allergy & Immunology (2012), 158(1), 1-8

Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between ... [more ▼]

Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control. Methods: We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor-alpha from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score <1.5; n = 20] and patients with uncontrolled asthma despite inhaled or oral corticoids (ACQ score >/=1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 mug/ml), and cytokines were measured by immunotrapping (ELISA). Results: Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-gamma release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines. Conclusion: Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation. [less ▲]

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See detail(Ex-)smoking asthma patients in general and specialized Belgian practice.
Decramer, M.; Louis, Renaud ULg; Joos, G. et al

in Respiratory medicine (2011), 105(8), 1203-1210

INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian ... [more ▼]

INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian practice both at the level of general practitioners (GPs) and specialists. MATERIALS AND METHODS: One hundred and nineteen smoking, non-smoking and ex-smoking patients (25-65 yrs) with asthma, COPD or both, were recruited by 33 GPs and 33 specialists. Data were obtained retrospectively from medical records. However, only a small number of files were complete. RESULTS: The majority of COPD patients were (ex-)smokers: 94% in the specialist group, 78% in the GP group. Cardiovascular comorbidity appeared in both groups in the same frequency order: COPD>(ex-)smoking patients with asthma (AS)>non-smoking patients with asthma (ANS), with a significant difference between AS and ANS in the specialist population. Chronic cough during more than 3 months in two consecutive years was reported in 97% of COPD patients, in 71% of the AS patients and in only 25% of the ANS patients. The type of cough differed between AS and ANS in the GP group, with a higher prevalence of productive cough in the former. Treatment patterns observed were as expected according to diagnosis except for a disproportionate use of Tiotropium in AS in the GP group. CONCLUSION: AS were somewhere in between COPD patients and ANS for a large number of the characteristics studied, suggesting that they are an intermediate phenotype between COPD and asthma. [less ▲]

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See detailSirtuin 1 Promotes Th2 Responses and Airway Allergy by Repressing Peroxisome Proliferator-Activated Receptor-γ Activity in Dendritic Cells
Legutko, Agnieszka; Marichal, Thomas ULg; Fievez, Laurence ULg et al

in Journal of Immunology (2011), 187(9), 4517-4529

Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have ... [more ▼]

Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have anti-inflammatory activities by inhibiting proinflammatory transcription factors such as NF-κB. In contrast, we report in this study that pharmacological inhibition of sirtuins dampens adaptive Th2 responses and subsequent allergic inflammation by interfering with lung dendritic cell (DC) function in a mouse model of airway allergy. Using genetic engineering, we demonstrate that sirtuin 1 represses the activity of the nuclear receptor peroxisome proliferator-activated receptor-γ in DCs, thereby favoring their maturation toward a pro-Th2 phenotype. This study reveals a previously unappreciated function of sirtuin 1 in the regulation of DC function and Th2 responses, thus shedding new light on our current knowledge on the regulation of inflammatory processes by sirtuins. [less ▲]

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