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Article Dans Une Revue Journal of Autoimmunity Année : 2022

Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases

Résumé

Inflammatory bowel disease (IBD) is a serious public health problem in Western society with a continuing increase in incidence worldwide. Safe, targeted medicines for IBD are not yet available. Autophagy, a vital process implicated in normal cell homeostasis, provides a potential point of entry for the treatment of IBDs, as several autophagy-related genes are associated with IBD risk. We conducted a series of experiments in three distinct mouse models of colitis to test the effectiveness of therapeutic P140, a phosphopeptide that corrects autophagy dysfunctions in other autoimmune and inflammatory diseases. Colitis was experimentally induced in mice by administering dextran sodium sulfate and 2,4,6 trinitrobenzene sulfonic acid. Transgenic mice lacking both il-10 and iRhom2 - involved in tumor necrosis factor α secretion - were also used. In the three models investigated, P140 treatment attenuated the clinical and histological severity of colitis. Post-treatment, altered expression of several macroautophagy and chaperone-mediated autophagy markers, and of pro-inflammatory mediators was corrected. Our results demonstrate that therapeutic intervention with an autophagy modulator improves colitis in animal models. These findings highlight the potential of therapeutic peptide P140 for use in the treatment of IBD.

Domaines

Cancer Immunologie

Dates et versions

hal-03632352 , version 1 (06-04-2022)

Identifiants

Citer

Sruthi Vijaya Retnakumar, Ramasatyaveni Geesala, Alexis Bretin, Julien Tourneur-Marsille, Eric Ogier-Denis, et al.. Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases. Journal of Autoimmunity, 2022, 128, pp.1-11. ⟨10.1016/j.jaut.2022.102814⟩. ⟨hal-03632352⟩
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