CE14 - Physiologie et physiopathologie

Tissue specificity of paradoxical effects of anti-TNF therapy in inflammatory bowel diseases – ANTIPODE

Paradoxical effects of anti-TNF in Crohn's disease

Systemic manifestations are a hallmark of chronic inflammatory diseases, as bone destruction in inflammatory bowel disease (IBD). Anti-TNF-a therapy is the first-line of treatment for IBD but despite its efficacy in the gut and bone, it induces psoriatic skin lesions. In addition of serious consequences for patient care, this side effect raises the question of the tissue specificity of the control of inflammatory responses that remains largely unknown.

Objectives

Our aims are to understand the specific response to anti-TNF-a in the gut, bone and skin focusing on environmental factors and on immune cells.

We will combine analysis in a murine IBD model mimicking what observed in patients +/- anti-TNF-a treatment and in IBD patients treated or not with anti-TNF therapy having or not psoriasis.

Analysis are ongoing

The results will open new clues for improving therapeutic approaches or prognosis markers for anti-TNF-a paradoxical effects and may impact other chronic diseases in which such effects are also reported

Madel et al Bixive 2020

Systemic manifestations are a hallmark of chronic inflammatory diseases, as for instance bone destruction in inflammatory bowel disease (IBD). Anti-TNF therapy is the first-line of treatment for IBD but despite its efficacy on gut inflammation and bone destruction, it induces psoriatic skin lesions. In addition of serious consequences for patient care, this side effect raises the question of the tissue specificity of the control of inflammatory responses that remains largely unknown. Our aims are to understand the specific response to anti-TNF in the gut, bone and skin focusing on environmental factors and on immune cells particularly IL-17 secreting cells (Th17 and ILC3). We will combine analysis in a murine IBD model mimicking what observed in patients +/- anti-TNF treatment and in IBD patients treated or not with anti-TNF therapy having or not psoriasis. The results will open new clues for improving therapeutic approaches or prognosis markers for anti-TNF paradoxical effects and may impact other chronic diseases in which such effects are also reported.

Project coordination

Abdelilah Wakkach (Laboratoire de Physio-Médecine Moléculaire)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LP2M Laboratoire de Physio-Médecine Moléculaire
Plateforme de Recherche sur les Maladies Inflammatoires Chroniques de l’Intestin
UMR7365 Ingénierie Moléculaire et Physiopathologie Articulaire
ICT Immunologie Immunopathologie et Chimie Thérapeutique (UPR 3572)

Help of the ANR 603,163 euros
Beginning and duration of the scientific project: December 2019 - 48 Months

Useful links

Explorez notre base de projets financés

 

 

ANR makes available its datasets on funded projects, click here to find more.

Sign up for the latest news:
Subscribe to our newsletter