References of "El Abbas, Sophie"
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See detailCharacterization and regulation of the intestinal epithelial cell response to colitogenic triggers
El Abbas, Sophie ULiege; Beguin, C; Schyns, Joey ULiege et al

in Proceedings of Annual meeting of the French Society for Immunology (SFI) (2017, November 07)

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See detailRab guanine nucleotide exchange factor 1 (Rabgef1) restricts intestinal inflammation by limiting pro-inflammatory signals in Intestinal Epithelial Cells (IECs)
El Abbas, Sophie ULiege; Beguin, Charline ULiege; Schyns, Joey ULiege et al

in Proceedings: 4th FARAH-DAY (2017, October 13)

Rab guanine nucleotide exchange factor (GEF-)1 (Rabgef1), a multifunctional protein whose in vivo functions remained unknown until recently, is highly expressed in mouse and human epithelial cells. The ... [more ▼]

Rab guanine nucleotide exchange factor (GEF-)1 (Rabgef1), a multifunctional protein whose in vivo functions remained unknown until recently, is highly expressed in mouse and human epithelial cells. The aim of this study is to investigate the role of Rabgef1 in intestinal epithelial cells (IECs) and intestinal homeostasis in mice. We performed conditional deletion of Rabgef1 gene using the cre-lox system to obtain mice lacking Rabgef1 specifically in IECs (Rabgef1IEC-KO), under the wild-type (WT) or the colitis-prone Interleukin-10 (Il-10)-deficient background. In addition, we used the CRISPR-Cas9 technology to obtain a murine IEC line deficient in Rabgef1. Rabgef1IEC-KO mice under the WT background did not develop spontaneous intestinal abnormalities but exhibited an altered intestinal microbial composition associated with minor changes in IEC pro-inflammatory gene expression profile. Moreover, Rabgef1IEC-KO mice exhibited an increased susceptibility to inflammation in a dextran sodium sulfate (DSS)-induced model of colitis under the WT background, as well as in a constitutive model of colitis under the Il-10-¬deficient background. In vitro, we showed that mouse IECs lacking Rabgef1 significantly overexpressed several pro-inflammatory cytokines and chemokines as compared to control cells. Taken together, these results support that Rabgef1 acts as a regulator of intestinal homeostasis and inflammation, and that dysregulated Rabgef1 expression could contribute to intestinal barrier dysfunction in inflammatory conditions of the gut. [less ▲]

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See detailEpithelial Rab guanine nucleotide exchange factor 1 (Rabgef1) deficiency increases susceptibility to DSS-induced intestinal inflammation in mice
El Abbas, Sophie ULiege; Beguin, C; Mesnil, Claire ULiege et al

in Proceedings: 3rd FARAH-DAY (2016, October 21)

Rab guanine nucleotide exchange factor (GEF)1 (Rabgef1) is a guanine nucleotide exchange factor for the endocytic GTPase Rab5, and also exhibits E3 ubiquitin ligase activity in vitro. In vivo functions of ... [more ▼]

Rab guanine nucleotide exchange factor (GEF)1 (Rabgef1) is a guanine nucleotide exchange factor for the endocytic GTPase Rab5, and also exhibits E3 ubiquitin ligase activity in vitro. In vivo functions of Rabgef1 remain largely unknown, but Rabgef1 is critical for health, as globally Rabgef1-deficient mice exhibit perinatal mortality and those surviving to adulthood spontaneously develop severe skin inflammation.This protein is highly expressed in murine intestinal epithelial cells (IECs). Objective: The aim of this study is to clarify the role of Rabgef1 in murine IECs Materials and methods: We performed conditional deletion of Rabgef1 using the cre-lox system to obtain mice lacking Rabgef1 specifically in IECs (Rabgef1IEC-KO). Results: Rabgef1IEC-KO mice did not develop spontaneous intestinal abnormalities but showed an increased susceptibility to inflammation in dextran sodium sulfate (DSS)-induced col itis model. Indeed, compared to littermate controls, mice lacking Rabgef1 in IECs exhibited shorter and highly inflamed colons and higher inflammatory scores in histopathological examination of colons, suggesting that Rabgef1 expression regulates IEC function and is critical in limiting DSS induced inflammation and damage. In addition, we also showed that mRNA expression of pro-inflammatory cytokines, such as Il1b and Tnfa, was upregulated in IECs isolated from Rabgef1IEC-KO mice compared to the ones isolated from littermate controls. Conclusion: Taken together, these results suggest that Rabgef1 acts as a regulator of intestinal homeostasis, and that dysregulated Rabgef1 expression could contribute to intestinal barrier dysfunction in inflammatory conditions of the gut. [less ▲]

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See detailEpithelial Rab guanine nucleotide exchange factor 1 (Rabgef1) deficiency increases susceptibility to DSS-induced intestinal inflammation in mice
El Abbas, Sophie ULiege; Beguin, C; Mesnil, Claire ULiege et al

Poster (2016, May 27)

Rab guanine nucleotide exchange factor (GEF)1 (Rabgef1) is a guanine nucleotide exchange factor for the endocytic GTPase Rab5, and also exhibits E3 ubiquitin ligase activity in vitro. In vivo functions of ... [more ▼]

Rab guanine nucleotide exchange factor (GEF)1 (Rabgef1) is a guanine nucleotide exchange factor for the endocytic GTPase Rab5, and also exhibits E3 ubiquitin ligase activity in vitro. In vivo functions of Rabgef1 remain largely unknown, but Rabgef1 is critical for health, as globally Rabgef1-deficient mice exhibit perinatal mortality and those surviving to adulthood spontaneously develop severe skin inflammation. In the mouse gut, we found that Rabgef1 is highly expressed in intestinal epithelial cells (IECs). We performed conditional deletion of Rabgef1 using the cre-lox system to obtain mice lacking Rabgef1 specifically in IECs (Rabgef1IEC-KO). These mice did not develop spontaneous intestinal abnormalities but showed an increased susceptibility to inflammation in dextran sodium sulfate (DSS)-induced colitis model. Indeed, compared to littermate controls, mice lacking Rabgef1 in IECs exhibited shorter and highly inflamed colons and higher inflammatory scores in histopathological examination of colons, suggesting that Rabgef1 expression regulates IEC function and is critical in limiting DSS induced inflammation and damage. In addition, we also showed that mRNA expression of pro-inflammatory cytokines, such as Il1b and Tnfa, was upregulated in IECs isolated from Rabgef1IEC-KO mice compared to the ones isolated from littermate controls. Taken together, these results suggest that Rabgef1 acts as a regulator of intestinal homeostasis, and that dysregulated Rabgef1 expression could contribute to intestinal barrier dysfunction in inflammatory conditions of the gut. [less ▲]

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See detailGuanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis.
Marichal, Thomas ULiege; Gaudenzio, Nicolas; El Abbas, Sophie ULiege et al

in Journal of Clinical Investigation (2016), 126(12), 4497-4515

Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we ... [more ▼]

Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we have found that keratinocyte-specific deletion of the gene encoding RAB guanine nucleotide exchange factor 1 (RABGEF1, also known as RABEX-5) severely impairs epidermal barrier function in mice and induces an allergic cutaneous and systemic phenotype. RABGEF1-deficient keratinocytes exhibited aberrant activation of the intrinsic IL-1R/MYD88/NF-kappaB signaling pathway and MYD88-dependent abnormalities in expression of structural proteins that contribute to skin barrier function. Moreover, ablation of MYD88 signaling in RABGEF1-deficient keratinocytes or deletion of Il1r1 restored skin homeostasis and prevented development of skin inflammation. We further demonstrated that epidermal RABGEF1 expression is reduced in skin lesions of humans diagnosed with either atopic dermatitis or allergic contact dermatitis as well as in an inducible mouse model of allergic dermatitis. Our findings reveal a key role for RABGEF1 in dampening keratinocyte-intrinsic MYD88 signaling and sustaining epidermal barrier function in mice, and suggest that dysregulation of RABGEF1 expression may contribute to epidermal barrier dysfunction in allergic skin disorders in mice and humans. Thus, RABGEF1-mediated regulation of IL-1R/MYD88 signaling might represent a potential therapeutic target. [less ▲]

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See detailCharacterisation of TLR7/8 in equine pulmonary alveolar macrophages
Tosi, Irène ULiege; Frellstedt, Linda; Pirottin, Dimitri ULiege et al

Poster (2015, October 08)

Purpose of the study: In both human and equine athletes, viral infections are common causes of respiratory diseases and of a sudden deterioration of expected performances. In both species, the underlying ... [more ▼]

Purpose of the study: In both human and equine athletes, viral infections are common causes of respiratory diseases and of a sudden deterioration of expected performances. In both species, the underlying mechanisms are still unclear, and an involvement of Toll-Like Receptors (TLRs), a fundamental link between innate and adaptive immunity, has been advocated. Our objectives were to verify the presence of TLR7 and TLR8, responsible for the early anti-viral response in mammals, in equine pulmonary alveolar macrophages (PAMs) and to assess their function through specific stimulation. Methods used: Equine PAMs were collected by broncho-alveolar lavage (BAL), isolated by adherence and stimulated with specific TLR7/8 ligands (an imidazoquinoline compound and single-stranded RNA), mimicking a viral attack. The expression of TLR7/8 was evaluated by rt-PCR and the ligand-induced production of cytokines (type I-IFNs and TNF-α) was assessed via ELISA. Summary of results: Our study demonstrated the expression of TLR7/8 in equine PAMs. QPCR analyses showed a high relative expression of genes coding for TLR7 and TLR8 on equine PAM. Stimulation with specific TLR7/8 ligands resulted in significantly up-regulated production of IFN-β and TNF-α, thereby confirming that TLR7/8 are functional in equine PAMs and that they play a role in the early pulmonary antiviral response. Conclusions: This study shows that TLR7 and TLR8 are present and functional in equine PAM and that they could play a role in the early pulmonary antiviral response. In terms of future perspectives, it is interesting to suggest that the extensively demonstrated efficacy of TLR7 and TLR8 synthetic ligands in the treatment of viral diseases in human medicine could motivate the pursuit of clinical trials in the equine patient for the therapeutic management or prevention of viral respiratory infections. [less ▲]

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See detailExperimental model of equine alveolar macrophage stimulation with TLR ligands.
Waldschmidt, Ingrid; Pirottin, Dimitri ULiege; Art, Tatiana ULiege et al

in Veterinary Immunology and Immunopathology (2013), 155(1-2), 30-37

Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate ... [more ▼]

Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate this response in horses are lacking. The aim of this study was to develop and validate an experimental model that could be applied in several physiological and pathological conditions to assess the innate immune response of equine pulmonary cells. Equine alveolar macrophages (AMs) obtained from bronchoalveolar lavages were isolated from other cells by adhesion. TLR2, 3, and 4 expression in AMs was studied and their responses to commercial ligands (respectively FSL-1, Poly(I:C), and LPS) were evaluated after determination of the appropriate dose and time of incubation. TLR responses were assessed by measuring cytokine production using (1) gene expression of TNFalpha, IFNbeta, Il-1beta, and IFNalpha by qPCR (indirect method); and (2) cytokine production for TNFalpha and IFNbeta by ELISA (direct method). TLR 2, 3, and 4 were expressed by AMs. TLR 2 stimulation with 10ng/mL of FSL-1 during 3h significantly increased IL-1beta and TNFalpha gene expression. TLR 3 stimulation with 1000ng/mL of Poly(I:C) during 1h increased IFNbeta, IFNalpha, Il-1beta and TNFalpha expression. TLR 4 stimulation with 100ng/mL of LPS during 3h increased TNFalpha, IFNbeta, and Il-1beta expression. Results obtained by ELISA quantification of TNFalpha and IFNbeta produced by AMs following stimulation during 6h were similar: FSL-1 increased TNFalpha production but not IFNbeta, Poly(I:C) and LPS increased production of IFNbeta and TNFalpha. In conclusion, pulmonary innate immunity of horses can be assessed ex vivo by measuring cytokine production following stimulation of AMs with TLR agonists. This experimental model could be applied under several conditions especially to improve the understanding of equine respiratory disease pathogenesis, and to suggest novel therapeutic opportunities. [less ▲]

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