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Titre : | Génération de cellules monocytaires THP-1 déficientes pour lexpression des protéines GasdermineDet WDFY4 pour létude du mécanisme de sécrétion de lIL-1B mature |
Auteurs : | Aïcha IMNADINE, Auteur ; Tiphanie Gomard, Promoteur |
Type de document : | Travail de fin d'études |
Editeur : | Bruxelles : Institut Paul Lambin, 2020 |
Langues: | Français |
Index. décimale : | TFE - Biologie médicale |
Résumé : |
Interleukin-1β (IL-1β) is a pro-inflammatory cytokine important for host-defence responses to infection and injury. The mature form of IL-1β does not contain a consensus signal sequence and is therefore secreted via an unconventional mechanism. Many secretion pathways have been proposed, including autophagy. The WDFY4 protein, not much studied, is implicated in unconventional autophagy and is highly expressed by human monocytic THP-1 cells.
The aim of this study is to test the implication of WDFY4 in the secretion of mature IL-1β. We used CRISPR/Cas9 technology to inactivate the WDFY4 gene leading to a cell deficient for this protein, to understand its role in IL-1β secretion. The protein Gasdermin D (GSDMD) is involved in an inflammatory cell death called pyroptosis. We know that this protein plays a role in the secretion of mature IL-1β. Despite a deficiency for Gasdermin D gene, mature IL-1β ends up being secreted. Another mechanism of secretion remains to be established. To better understand this secretion mechanism without the role of gasdermine D we used THP-1, deficient for Gasdermin D (THP-1 GSDMD-/-), in which we invalidated gene WDFY4 and study IL-1 secretion after LPS stimulation. The results show that GSDMD-/- -WDFY4-/- THP-1 cells secrete only very small amounts of IL-1β contrary to what we are used to see. However, the cytokine still ends up being secreted despite the invalidation of gene WDFY4. Thus the Gasdermin D-independent mechanism of secretion of IL-1β is also independent from unconventional autophagy. |
Accès : | Identifiez-vous avant d'accéder au document électronique |
Disponible en ligne : | Oui |
Lieu du stage : | UCL -Institut de Duve (ICP) - Pôle de génétique cellulaire (GECE) |
Département : | Biologie médicale |
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TFE biologie médicale Adobe Acrobat PDF |