Presentation

Phagocytes, NADPH oxidases and immunogenetics in systemic inflammation.

Jamel El Benna
Team Leader

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Our team is interested in studying molecular and cellular mechanisms of inflammation, focusing on the regulationof the main reactive oxygen species (ROS) producing enzymes, the NADPH oxidases (NOXs) and their role in thephysiopathology of inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD). When their production is controlled, reactive oxygen species (ROS) are involved in many important physiological functions. Thus ROS produced by the phagocyte NADPH oxidase, NOX2, in neutrophils, monocytes and macrophages are required for their bactericidal function, and importantly in dendritic cells, NOX2 has a critical role in antigen cross-presentation. Homologues of NOX2, such as NOX1, are also expressed in epithelial cells, but their physiological role is not fully understood. On the other hand, it is clear that excessive or inappropriate ROS production can induce severe tissue injury that participates to the physiopathology of inflammatory diseases. Deciphering mechanisms underlying activation of NOX2 in phagocytes and NOX1 in epithelial cells is essential to identify novel therapeutic targets in inflammation. The projects of the team aim to understand the regulation of NOX2 in neutrophils, monocytes/macrophages and dendritic cells and NOX1 in epithelial cells by pro- and anti-inflammatory agents; and to translate our basic research to animal models of inflammation, human phagocytic disorders and human inflammatory diseases. Our project combines basic and clinical research and involves several collaborations with teams in the Center for Research on Inflammation (CRI) and Bichat hospital divisions.

 

Principal research axis:

Our work is conducted following three main axis : 1)-To understand the regulation of the NADPH oxidases NOX in neutrophils, monocytes, macrophages, dendritic cells and epithelial cells in response to pro- and anti-inflammatory agents. 2)-To study polymorphism of NOX and regulators and identify new genetic factors involved in systemic inflammation. 3-To study the role of the NOX2, NOX1 and newly identified proteins in inflammatory process: by investigating their activation in phagocytic disorders, human inflammatory diseases and in animal models of inflammation.

illustrations

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Selected publications
  • Makhezer N, Ben Khemis M, Liu D, Khichane Y, Marzaioli V, Tlili A, Mojallali M, Pintard C, Letteron P, Hurtado-Nedelec M, El-Benna J, Marie JC, Sannier A, Pelletier AL, Dang PM. NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions. Mucosal Immunology, 2018 Oct doi: 10.1038/s41385-018-0086-4. [Epub ahead of print] PubMed PMID: 30279516.
  • Rolas L, Boussif A, Weiss E, Lettéron P, Haddad O, El-Benna J, Rautou PE, Moreau R, Périanin A. NADPH oxidase depletion in neutrophils from patients with cirrhosis and restoration via toll-like receptor 7/8 activation. Gut. 2018;67(8):1505-1516.
  • Marzaioli V, Hurtado-Nedelec M, Pintard C, Tlili A, Marie JC, Monteiro R, Gougerot-Pocidalo MA, Dang PM, El-Benna J. NOX5 and p22phox are two novel regulators of human monocytic differentiation into dendritic cells. Blood. 2017 Oct 12;130(15):1734-1745.
  • Chedid P, Boussetta T, Dang PM, Belambri SA, Marzaioli V, Fasseau M, WalkerF, Couvineau A, El-Benna J, Marie JC. Vasoactive intestinal peptide dampens formyl-peptide-induced ROS production and inflammation by targeting a MAPK-p47(phox) phosphorylation pathway in monocytes. Mucosal Immunology, 2017 Mar;10(2):332-340.
  • El-Benna J, Hurtado-Nedelec M, Marzaioli V, Marie JC, Gougerot-Pocidalo MA, Dang PM. Priming of the neutrophil respiratory burst : Role in host defense and inflammation. Immunological Reviews, 2016 Sep;273(1):180-93.
Team members
Team leader Jamel El Benna, DR 
Researchers Pham My-Chan Dang, DR
  Jamel El Benna, DR
  Maria-Margarita Hurtado-Nedelec, MCUPH
  Marie-Anne Gougerot-Pocidalo, PHU-E
  Axel Periani, DR-E
Engeneers and technicians Coralie Pintard, AI
PhD Students Hansnaa Maksouri
Rhana Nassif
Marwah Ben-Kemis
Dan Liu
Min Liu
Amina Chniguir
M2 Students
Marjan Mojallali
Amira Haj-Dahmane
Yasmina Midoune
M1 Students
ines Bakhti