References of "Desmet, Christophe"
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See detailWobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.
Rapino, Francesca ULiege; ZHOU, ZHAOLI; RONCERO SANCHEZ, Ana Maria et al

in Nature Communications (2021), 12(1), 2170

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon ... [more ▼]

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcm(5)s(2) wobble uridine tRNA modification (U(34)-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U(34)-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U(34)-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis. [less ▲]

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See detailLoss of tRNA-modifying enzyme Elp3 activates a p53-dependent antitumor checkpoint in hematopoiesis.
Rosu, Adeline ULiege; El Hachem, Najla ULiege; Rapino, Francesca ULiege et al

in The Journal of experimental medicine (2021), 218(3),

The hematopoietic system is highly sensitive to perturbations in the translational machinery, of which an emerging level of regulation lies in the epitranscriptomic modification of transfer RNAs (tRNAs ... [more ▼]

The hematopoietic system is highly sensitive to perturbations in the translational machinery, of which an emerging level of regulation lies in the epitranscriptomic modification of transfer RNAs (tRNAs). Here, we interrogate the role of tRNA anticodon modifications in hematopoiesis by using mouse models of conditional inactivation of Elp3, the catalytic subunit of Elongator that modifies wobble uridine in specific tRNAs. Loss of Elp3 causes bone marrow failure by inducing death in committing progenitors and compromises the grafting activity of hematopoietic stem cells. Mechanistically, Elp3 deficiency activates a p53-dependent checkpoint in what resembles a misguided amino acid deprivation response that is accompanied by Atf4 overactivation and increased protein synthesis. While deletion of p53 rescues hematopoiesis, loss of Elp3 prompts the development of p53-mutated leukemia/lymphoma, and inactivation of p53 and Elongator cooperatively promotes tumorigenesis. Specific tRNA-modifying enzymes thus condition differentiation and antitumor fate decisions in hematopoietic stem cells and progenitors. [less ▲]

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See detailLoss of the Transfer RNA Wobble Uridine-Modifying Enzyme Elp3 Delays T Cell Cycle Entry and Impairs T Follicular Helper Cell Responses through Deregulation of Atf4.
Lemaitre, Pierre ULiege; Bai, Qiang ULiege; Legrand, Céline ULiege et al

in Journal of immunology (Baltimore, Md. : 1950) (2021)

The activation of T cells is accompanied by intensive posttranscriptional remodeling of their proteome. We observed that protein expression of enzymes that modify wobble uridine in specific tRNAs, namely ... [more ▼]

The activation of T cells is accompanied by intensive posttranscriptional remodeling of their proteome. We observed that protein expression of enzymes that modify wobble uridine in specific tRNAs, namely elongator subunit 3 (Elp3) and cytosolic thiouridylase (Ctu)2, increased in the course of T cell activation. To investigate the role of these tRNA epitranscriptomic modifiers in T cell biology, we generated mice deficient for Elp3 in T cells. We show that deletion of Elp3 has discrete effects on T cells. In vitro, Elp3-deficient naive CD4(+) T cells polarize normally but are delayed in entering the first cell cycle following activation. In vivo, different models of immunization revealed that Elp3-deficient T cells display reduced expansion, resulting in functional impairment of T follicular helper (TFH) responses, but not of other CD4(+) effector T cell responses. Transcriptomic analyses identified a progressive overactivation of the stress-responsive transcription factor Atf4 in Elp3-deficient T cells. Overexpression of Atf4 in wild-type T cells phenocopies the effect of Elp3 loss on T cell cycle entry and TFH cell responses. Reciprocally, partial silencing of Atf4 or deletion of its downstream effector transcription factor Chop rescues TFH responses of Elp3-deficient T cells. Together, our results reveal that specific epitranscriptomic tRNA modifications contribute to T cell cycle entry and promote optimal TFH responses. [less ▲]

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See detailIdentification of pro-fibrotic macrophage populations by single-cell transcriptomic analysis in West Highland white terriers affected with canine idiopathic pulmonary fibrosis.
Fastrès, Aline ULiege; Pirottin, Dimitri ULiege; Fievez, Laurence ULiege et al

in Frontiers in Immunology (2020), 11

Canine idiopathic pulmonary fibrosis (CIPF) affects old dogs from the West Highland white terrier (WHWT) breed and mimics idiopathic pulmonary fibrosis (IPF) in human. The disease results from deposition ... [more ▼]

Canine idiopathic pulmonary fibrosis (CIPF) affects old dogs from the West Highland white terrier (WHWT) breed and mimics idiopathic pulmonary fibrosis (IPF) in human. The disease results from deposition of fibrotic tissue in the lung parenchyma causing respiratory failure. Recent studies in IPF using single-cell RNA sequencing (scRNA-seq) revealed the presence of profibrotic macrophage populations in the lung, which could be targeted for therapeutic purpose. In dogs, scRNA-seq was recently validated for the detection of cell populations in bronchoalveolar lavage fluid (BALF) from healthy dogs. Here we used the scRNA-seq to characterize disease-related heterogeneity within cell populations of macrophages/monocytes (Ma/Mo) in the BALF from 5 WHWTs affected with CIPF in comparison with 3 healthy WHWTs. Gene set enrichment analysis was also used to assess pro-fibrotic capacities of Ma/Mo populations. Five clusters of Ma/Mo were identified. Gene set enrichment analyses revealed the presence of pro-fibrotic monocytes in higher proportion in CIPF WHWTs than in healthy WHWTs. In addition, monocytes-derived macrophages enriched in pro-fibrotic genes in CIPF compared with healthy WHWTs were also identified. These results suggest the implication of Ma/Mo clusters in CIPF processes, although, further research is needed to understand their role in disease pathogenesis. Overexpressed molecules associated with pulmonary fibrosis processes were also identified that could be used as biomarkers and/or therapeutic targets in the future. [less ▲]

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See detailIdentification of pro-fibrotic macrophages populations by single-cell transcriptomic analysis in West Highland white terriers affected with canine idiopathic pulmonary fibrosis.
Fastrès, Aline ULiege; Pirottin, Dimitri ULiege; Fievez, Laurence ULiege et al

Scientific conference (2020, November 20)

Canine idiopathic pulmonary fibrosis (CIPF) is a not well understand disease which affects old West Highland white terriers (WHWTs) and mimics idiopathic pulmonary fibrosis (IPF) in man. Recent studies in ... [more ▼]

Canine idiopathic pulmonary fibrosis (CIPF) is a not well understand disease which affects old West Highland white terriers (WHWTs) and mimics idiopathic pulmonary fibrosis (IPF) in man. Recent studies in IPF using the single-cell RNA sequencing (scRNA-seq) technique revealed the presence of profibrotic macrophages populations in the lung. Here we used the scRNA-seq to characterize disease-related heterogeneity within cell subsets of macrophages/monocytes (Ma/Mo) in the BALF of 5 WHWTs affected with CIPF in comparison with 3 healthy WHWTs. Five subsets of Ma/Mo were identified. Among them, a monocytes subset present in larger proportion in CIPF WHWTs showed a gene expression profile enriched for pulmonary fibrosis processes (PFPs) (normalized enrichment score (NES) = 1.85, q-value = 0.002). Eight genes associated with PFPs were significantly overexpressed in this subset including CCL2, SPP1, FN1, CCL3, TIMP1, IL1RN, CXCL8 and CCL4. A monocytes-derived macrophages subset enriched for PFPs (NES = 1.87, q-value = 0.007) was also identified with differentially expressed genes between CIPF and healthy WHWTs. Expression in CIPF dogs in this subset was enriched for PFPs (NES = 2.01, q-value = 0.008) with significant overexpression of 4 genes associated with PFPs including FN1, SPP1, CXCL8 and PLAU. ScRNA-seq analysis of BALF specimens from healthy and CIPF WHWTs identified pro-fibrotic Ma/Mo populations enriched in pro-fibrotic genes suggesting the implication of these subpopulations in CIPF processes. Overexpressed molecules were also identified that could be used as biomarkers and/or therapeutic targets in the future. [less ▲]

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See detailAdvances toward precision medicine for asthma
Louis, Renaud ULiege; Bureau, Fabrice ULiege; Desmet, Christophe ULiege

in Biochemical Pharmacology (2020), 179

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See detailCharacterization of the bronchoalveolar lavage fluid by single cell gene expression analysis in healthy dogs: a promising technique.
Fastrès, Aline ULiege; Pirottin, Dimitri ULiege; Fievez, Laurence ULiege et al

in Frontiers in Immunology (2020), 11

Single-cell mRNA-sequencing (scRNA-seq) is a technique which enables unbiased, high throughput and high-resolution transcriptomic analysis of the heterogeneity of cells within a population. This recent ... [more ▼]

Single-cell mRNA-sequencing (scRNA-seq) is a technique which enables unbiased, high throughput and high-resolution transcriptomic analysis of the heterogeneity of cells within a population. This recent technique has been described in humans, mice and other species in various conditions to cluster cells in populations and identify new subpopulations, as well as to study the gene expression of cells in various tissues, conditions and origins. In dogs, a species for which markers of cell populations are often limiting, scRNA-seq presents with elevated yet untested potential for the study of tissue composition. As a proof of principle, we used scRNA-seq to identify cellular populations of the bronchoalveolar lavage fluid (BALF) in healthy dogs (n = 4). A total of 5710 cells were obtained and analyzed by scRNA-seq. Fourteen distinct clusters of cells were identified, further identified as macrophages/monocytes (4 clusters), T cells (2 clusters) and B cells (1 cluster), neutrophils (1 cluster), mast cells (1 cluster), mature or immature dendritic cells (1 cluster each), ciliated or non-ciliated epithelial cells (1 cluster each) and cycling cells (1 cluster). We used for the first time in dogs the scRNA-seq to investigate cellular subpopulations of the BALF of dog. This study hence expands our knowledge on dog lung immune cell populations, paves the way for the investigation at single-cell level of lower respiratory diseases in dogs, and establishes that scRNA-seq is a powerful tool for the study of dog tissue composition. [less ▲]

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See detailCharacterization of the bronchoalveolar lavage fluid by single cell gene expression analysis in healthy dogs: a promising technique.
Fastrès, Aline ULiege; Pirottin, Dimitri ULiege; Fievez, Laurence ULiege et al

in Journal of Veterinary Internal Medicine (2020), 34(6),

Single‐cell mRNA‐sequencing (scRNA‐seq) is a technique which enables unbiased, high throughput and high‐resolution transcriptomic analysis of the heterogeneity of cells within a population. This recent ... [more ▼]

Single‐cell mRNA‐sequencing (scRNA‐seq) is a technique which enables unbiased, high throughput and high‐resolution transcriptomic analysis of the heterogeneity of cells within a population. This recent technique has been described in humans, mice and other species in various conditions to cluster cells in populations and identify new subpopulations, as well as to study the gene expression of cells in various tissues, conditions and origins. In dogs, a species for which markers of cell populations are often limiting, scRNA‐seq presents with elevated yet untested potential for the study of tissue composition. As a proof of principle, we used scRNA‐seq to identify cellular populations of the bronchoalveolar lavage fluid (BALF) in healthy dogs (n = 4). Cells in suspension isolated from fresh BALF were loaded into the ChromiumTM and were directly encapsulated with unique barcoded primers using the drop‐sequencing method. Cells were lysed and reverse transcription of mRNAs took place into vesicles. cDNA was amplified after the breakage of the vesicles and sequenced on an Illumina NextSeq500. The analysis of the results and statistical analysis were performed using Cell Ranger software (v1.2.0), Seurat package in RStudio (v3.1.2) and the gene set enrichment analysis tool (GSEA‐P). A total of 5710 cells were obtained and analyzed. Fourteen distinct clusters of cells were identified, further identified as alveolar macrophages (AMs) (3 clusters) and monocytes‐derived macrophages (1 cluster). The first cluster of AMs composed by the majority of cells exerted functions involved in immune defense and response, the second cluster exerted functions involved in immune response regulation and the third exerted functions involved in metal ions homeostasis. Clusters of CD8+ and CD4+ T cells were also found (1 cluster each) as well as clusters of mature and immature dendritic cells (1 cluster each) and clusters of ciliated or non‐ciliated epithelial cells (1 cluster each). Finally, subpopulations of B cells, neutrophils, basophils and cycling cells were also identified (1 cluster each). We used for the first time in dogs the scRNA‐seq to investigate cellular subpopulations of the BALF. This study hence expands our knowledge on dog lung immune cell populations, paves the way for the investigation at single‐cell level of lower respiratory diseases in dogs, and establishes that scRNA‐seq is a powerful tool for the study of dog tissue composition. [less ▲]

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See detailEosinophil diversity in asthma
Van Hulst, Glenn ULiege; Batugedara, Hashini Maneesha ULiege; Jorssen, Joseph ULiege et al

in Biochemical Pharmacology (2020), 179

Eosinophils are a type of granulated innate immune cells that have long been implicated in a specific type of asthma, referred to as eosinophilic asthma. Several immunotherapeutics that target and deplete ... [more ▼]

Eosinophils are a type of granulated innate immune cells that have long been implicated in a specific type of asthma, referred to as eosinophilic asthma. Several immunotherapeutics that target and deplete eosinophils or limit their numbers are currently widely used and provide improved disease outcome in severe eosinophilic asthma. Current clinical results provide conclusive evidence of a generally detrimental role of eosinophils in asthma. Yet, a small but growing body of reports suggests that eosinophils may be more diverse than currently appreciated. In this review, we explore pre-clinical and clinical evidence that suggests the existence of eosinophil subsets with potentially distinct functional roles in asthma. We conclude by discussing state-of-the-art strategies for deciphering heterogeneity of this complex cell type, and argue this knowledge could translate into the improved personalized treatment of severe eosinophilic asthma. © 2020 Elsevier Inc. [less ▲]

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See detailThe phosphoinositide 5-phosphatase INPP5K: from gene structure to in vivo functions
Schurmans, Stéphane ULiege; Vande Catsyne, Charles-Andrew ULiege; Desmet, Christophe ULiege et al

in Advances in Biological Regulation (2020)

INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is ... [more ▼]

INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is comprised of a N-terminal catalytic domain which hydrolyses both PtdIns(4,5)P2 and PtdIns(3,4,5)P3, followed by a SKICH domain at the C-terminus which is responsible for protein-protein interactions and subcellular localization of INPP5K. Strikingly, INPP5K is mostly concentrated in the endoplasmic reticulum, although it is also detected at the plasma membrane, in the cytosol and the nucleus. Recently, mutations in INPP5K have been detected in patients with a rare form of autosomal recessive congenital muscular dystrophy with cataract, short stature and intellectual disability. INPP5K functions extend from control of insulin signaling, endoplasmic reticulum stress response and structural integrity, myoblast differentiation, cytoskeleton organization, cell adhesion and migration, renal osmoregulation, to cancer. The goal of this review is thus to summarize and comment recent and less recent data in the literature on INPP5K, in particular on the structure, expression, intracellular localization, interactions and functions of this specific member of the 5-phosphatases family. [less ▲]

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See detailEpithelial RABGEF1 deficiency promotes intestinal inflammation by dysregulating intrinsic MYD88-dependent innate signaling.
El Abbas, Sophie ULiege; Radermecker, Coraline ULiege; Bai, Qiang ULiege et al

in Mucosal Immunology (2019)

Intestinal epithelial cells (IECs) contribute to the regulation of intestinal homeostasis and inflammation through their interactions with the environment and host immune responses. Yet our understanding ... [more ▼]

Intestinal epithelial cells (IECs) contribute to the regulation of intestinal homeostasis and inflammation through their interactions with the environment and host immune responses. Yet our understanding of IEC-intrinsic regulatory pathways remains incomplete. Here, we identify the guanine nucleotide exchange factor RABGEF1 as a regulator of intestinal homeostasis and innate pathways dependent on IECs. Mice with IEC-specific Rabgef1 deletion (called Rabgef1(IEC-KO) mice) developed a delayed spontaneous colitis associated with the local upregulation of IEC chemokine expression. In mouse models of colitis based on Interleukin-10 deficiency or dextran sodium sulfate (DSS) exposure, we found that IEC-intrinsic RABGEF1 deficiency exacerbated development of intestinal pathology and dysregulated IEC innate pathways and chemokine expression. Mechanistically, we showed that RABGEF1 deficiency in mouse IECs in vitro was associated with an impairment of early endocytic events, an increased activation of the p38 mitogen-activated protein kinase (MAPK)-dependent pathway, and increased chemokine secretion. Moreover, we provided evidence that the development of spontaneous colitis was dependent on microbiota-derived signals and intrinsic MYD88-dependent pathways in vivo. Our study identifies mouse RABGEF1 as an important regulator of intestinal inflammation, MYD88-dependent IEC-intrinsic signaling, and chemokine production. This suggests that RABGEF1-dependent pathways represent interesting therapeutic targets for inflammatory conditions in the gut. [less ▲]

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See detailGrowth hormone (GH) deficient mice with GHRH ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae
Farhat, Khalil; Bodart, Gwennaëlle ULiege; Charlet-Renard, Jeanne de Chantal ULiege et al

in Frontiers in Immunology (2018), 9

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene ... [more ▼]

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene (Ghrh−/−) have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of Ghrh−/− mice against S. pneumoniae, a pathogen carrying T-independent antigens. Ghrh−/− mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, PPV23) or protein-PPS conjugate (PCV13). GH supplementation of Ghrh−/− mice restored IgM response to PPV23 vaccine but not to PCV13 suggesting that GH could exert a specific impact on the spleen marginal zone that is strongly implicated in T-independent response against pneumococcal polysaccharides. As expected, after administration of low dose of S. pneumoniae, wild type (WT) completely cleared bacteria after 24 h. In marked contrast, Ghrh−/− mice exhibited a dramatic susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load and a lethal bacteraemia already after 24 h. Lungs of infected Ghrh−/− mice were massively infiltrated by inflammatory macrophages and neutrophils, while lung B cells were markedly decreased. The inflammatory transcripts signature was significantly elevated in Ghrh−/− mice. In this animal model, the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in vaccine and immunological defense against S. pneumoniae. [less ▲]

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See detailHuman papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation
Van hede, Dorien ULiege; Polese, Barbara ULiege; Humblet, Chantal ULiege et al

Poster (2018, June)

Background: γδ T cells have been shown to protect against the formation of squamous cell carcinoma (SCC) in several models. Yet, the role of γδ T cells in human papillomavirus (HPV) associated uterine ... [more ▼]

Background: γδ T cells have been shown to protect against the formation of squamous cell carcinoma (SCC) in several models. Yet, the role of γδ T cells in human papillomavirus (HPV) associated uterine cervical SCC, the third cause of death by cancer in women, is unknown. Method: We investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16-oncoproteins. Human uterine cervical biopsies of women infected by HPV were also analyzed. Results: Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16-oncoproteins induced a decrease in epidermal Skint1 expression and the associated anti-tumor Vγ5+ γδ T cells, which were replaced by γδ T cell subsets (mainly Vγ6+ γδlowCCR2+CCR6-) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A+ γδ T cells could be only observed at the cancer stage (SCC), where HPV-oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16-oncoproteins induce a reorganization of the local epithelial-associated γδ T cell subpopulations thereby promoting angiogenesis and cancer development. [less ▲]

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See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

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See detailGHRH-deleted Mice Are Severely Deficient in Vaccine And Immunological Responses Against Streptococcus Pneumoniae
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Desmet, Christophe ULiege et al

Conference (2018, March 20)

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions ... [more ▼]

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions, thymus and T-cell development are not severely affected but a marked spleen atrophy and B-cell lymphopenia were constantly observed (3). Therefore, we investigated vaccinal and anti-infectious responses of Ghrh-/- mice against S.pneumoniae, a T-independent pathogen. Results. Transgenic mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, Pnx23) or protein-PPS conjugate (Prev13). GH treatment of Ghrh-/- mice restored IgM response to Pnx23 vaccine but not to Prev13 suggesting that GH exerts a significant impact on the spleen marginal zone that is strongly implicated in T-independent immunological response to pneumococcal polysaccharides. After intranasal instillation of a non-lethal dose of S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility with a time-dependent increase in lung bacterial load, a bacteremia already after 24h, and a survival limit of 48-72h. In marked contrast, WT and heterozygote mice completely cleared S.pneumoniae infection after 24h. Lungs of infected Ghrh-/- mice were massively infiltrated by inflammatory macrophages, while lung B cells were markedly decreased. Transcription of Ifng, Il10, Cd40, and Cxcl9 was highly increased in the lungs of infected Ghrh-/- mice, whereas Tgfb and Iggj transcripts were unchanged. Resistance of Ghrh-/- mice to infection by influenzavirus H1N1 (a T-dependent antigen) was normal or slightly decreased. Conclusion. This animal model shows that the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in the vaccine and immunological defense against S.pneumoniae. [less ▲]

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See detailThe interstitial macrophage: A long-neglected piece in the puzzle of lung immunity
Liégeois, Maude ULiege; Legrand, Céline ULiege; Desmet, Christophe ULiege et al

in Cellular Immunology (2018), 330

Lung macrophages have mostly been studied considering only their most accessible and well-de fined representative, the alveolar macrophage (AM). In contrast, the identity and putative immune functions of ... [more ▼]

Lung macrophages have mostly been studied considering only their most accessible and well-de fined representative, the alveolar macrophage (AM). In contrast, the identity and putative immune functions of their tissue counterpart, the interstitial macrophage (IM), have long remained much more elusive. Yet, recent evidence supports the notion that IMs perform important immune functions in the lung, notably in terms of innate immunoregulation. Here, we review current knowledge on the phenotype, ontogeny and function of IMs and propose strategies for the unambiguous identification and study of this important and dynamic lung innate immune cell population [less ▲]

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See detailL’expérimentation animale reste indispensable (OPINION)
Amorim, Christiani; Andris, Fabienne; Arckens, Lut et al

Article for general public (2017)

Trop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle.

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaëlle ULiege; RENARD, Jeanne de Chantal ULiege et al

Poster (2017, May 23)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Renard, chantal et al

Poster (2017, May)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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