Skip to Main content Skip to Navigation
Theses

Etude des mécanismes d'actions de SuperMApo dans un modèle de sclérose en plaques

Abstract : Multiple sclerosis (MS) is an autoimmune disease notably delined bv a default of mechanisms of tissue reparation which are insufficient to establish homeostasis. The active resolution of innammation mediated by macrophage effcrocytosis of apoptotic cells has emerged to propose a new branch of pharmacology named "resolution pharmacology". ln this study. we propose to resolve innammation in a murine model of MS. using the supermatanl issued from the culture between apoptotic cells and macrophages. inducing efferocytosis and the production of pro-resolutive factors (SuperMApo). Here. we demonstrate that injection of SupcrMApo in a model of MS allow the control of the disease correlated with a reduction of the inflammatory inliltrate in the central nervous system. The control of the disease is associated with a reprograrnming of macrophages and pDC, but not cDC, in the spleen, demonstrated by a higher capacity to generate Treg and a lower ability to generate Th 1, and their presence is necessary to the anti-innammatory effect of SupcrMApo. Reprogramming of macrophages and pDC occurs at two main levels. First. an epigenetic control of gene expression induces a modulation of global DNA methylation and a modulation of DNA methylation at the promoter of miRNA implicated in the regulation of immune responses. Secondly, a decreased activation of NFκB activation pathway is observed resulting to a decreased activation of these cells. Thus, this work demonstrates that targeting the resolution of inflammation is an interesting strategy to treat MS.
Complete list of metadatas

Cited literature [546 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-02319441
Contributor : Abes Star :  Contact
Submitted on : Friday, October 18, 2019 - 1:02:57 AM
Last modification on : Friday, October 23, 2020 - 5:04:47 PM
Long-term archiving on: : Sunday, January 19, 2020 - 1:08:07 PM

File

these_A_GAUTHIER_Thierry_2017....
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-02319441, version 1

Collections

Citation

Thierry Gauthier. Etude des mécanismes d'actions de SuperMApo dans un modèle de sclérose en plaques. Immunologie. Université Bourgogne Franche-Comté, 2017. Français. ⟨NNT : 2017UBFCE010⟩. ⟨tel-02319441⟩

Share

Metrics

Record views

251

Files downloads

462