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Liens entre inflammations articulaire et digestive : étude expérimentale chez la souris et contribution de l’immunité mucosale

Abstract : Numerous type 3 immune cells (Th17 and ILC3) are physiologically located in lamina propria of the intestine. Microbial agents within the gut shape the immune system to make it efficient against threats but peaceful with commensals. Recent studies demonstrated changes in gut microbiota composition (dysbiosis) in chronic inflammatory rheumatism. These results suggest a role for mucosal immunity alteration in articular inflammation occurrence. Indeed, some type 3 immune cells once activated by microbiota, are thought to migrate to joints, involving notably chemokines receptors. Transcription factor RORγt, the master regulator of type 3 immune cells, could be negatively regulated by nuclear receptor PPARγ. Using experimental murine models, we studied the consequence of PPARγ deficiency and consequence of the chemokine receptor CCR3 inhibition on the joint-gut axis. Firstly, we demonstrated that experimental colitis induces microbiota changes, delays and reduces collagen-induced arthritis severity. Secondly, we showed that PPARγ deficient mice display spontaneous joint inflammation associated with abnormal type 3 distribution within the gut. Dysbiosis with enrichment in facultative anaerobic Enterobacteriaceae was found in these mice. Fecal microbiota transfer demonstrated this microbiota is non-arthritogenic. Finally, we demonstrated that CCR3 inhibition has profound anti-arthritic potencies associated with changes in leukocytes distribution within the joint-gut axis
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  • HAL Id : tel-01870524, version 1

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Julie Hablot. Liens entre inflammations articulaire et digestive : étude expérimentale chez la souris et contribution de l’immunité mucosale. Immunologie. Université de Lorraine, 2018. Français. ⟨NNT : 2018LORR0095⟩. ⟨tel-01870524⟩

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