PARP2 deficiency affects invariant-NKT-cell maturation and protects mice from Concanavalin A-induced liver injury.
Fiche publication
Date publication
juillet 2017
Journal
American journal of physiology. Gastrointestinal and liver physiology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DANTZER Françoise
Tous les auteurs :
Filliol A, Piquet-Pellorce C, Dion S, Genet V, Lucas-Clerc C, Dantzer F, Samson M
Lien Pubmed
Résumé
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during Concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells which promote inflammation and induce hepatocyte death, mediated by the activated invariant NKT-(iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs such as spleen, thymus, and bone marrow in Parp2 deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that i) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; ii) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2(-/-) mice; iii) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis.
Mots clés
Parp, autoimmune hepatitis, hepatitis, liver, natural killer T cells
Référence
Am. J. Physiol. Gastrointest. Liver Physiol.. 2017 Jul;:ajpgi.00436.2016