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You are here: Home / About us / News / Autophagy, a key role in the pathophysiology of Crohn's disease

Autophagy, a key role in the pathophysiology of Crohn's disease

In a new study published in the journal Autophagy, CIRI researchers have shown for the first time that, in patients with Crohn's disease, the expression of autophagic gene variants strongly affects autophagic dynamics, known as autophagic flux.

Crohn's disease is a chronic inflammatory bowel disease affecting several million people worldwide, with an increasing incidence in developed and newly industrialized countries. The disease is characterized by alternating periods of relapses and remissions, the onset of complications and the development of resistance to treatment. All of these events remain unpredictable, which calls for a much better understanding of the cellular and molecular elements involved in this pathology, in the hope of improving diagnosis, management and treatment of patients.

Genomic studies have identified a number of risk alleles, particularly those linked to autophagy, a cellular function essential to all cells in the body. Autophagy plays a crucial role in maintaining the balance and functionality of the body's cells (cellular homeostasis). It is also central to the immune response, enabling the degradation of intracellular microorganisms, for example, or regulating the intensity of inflammatory responses.

Nevertheless, despite the identification of these at-risk alleles, no data has ever really demonstrated the impact of autophagic gene polymorphism on autophagic activity in Crohn's patients.

To answer this question, researchers at the Centre International de Recherche en Infectiologie (CIRI - Inserm/UCBL/CNRS/ENS de Lyon) have developed a new approach. By precisely measuring the dynamic properties of autophagic flow in cells from Crohn's disease patients, they have identified for the first time an autophagic flow defect in patients expressing a polymorphism affecting an autophagy gene.

“In these patients, the level of autophagy is reduced, as is the rate at which cytosolic elements are degraded”, explains Aurore Rozières (Maîtresse de Conférences at UCBL), who led this work.

This study, published in Autophagy, is the first to characterize autophagic flux from patient cells, and opens up important prospects for understanding Crohn's disease and the possible identification of new molecular targets for diagnosis and/or future treatments.

 

Credits: Mathieu Martin - Université Claude Bernard Lyon 1

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