PARP2 deficiency affects invariant-NKT,-cell maturation and protects mice from ,Concanavalin A-induced liver injury. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue AJP - Gastrointestinal and Liver Physiology Année : 2017

PARP2 deficiency affects invariant-NKT,-cell maturation and protects mice from ,Concanavalin A-induced liver injury.

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 natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the 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 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice; 3) 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.NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice
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Dates et versions

hal-01630440 , version 1 (07-11-2017)

Identifiants

Citer

Aveline Filliol, Claire Piquet-Pellorce, Sarah Dion, Valentine Genet, Catherine Lucas-Clerc, et al.. PARP2 deficiency affects invariant-NKT,-cell maturation and protects mice from ,Concanavalin A-induced liver injury.. AJP - Gastrointestinal and Liver Physiology, 2017, 313 (5), pp.G399-G409. ⟨10.1152/ajpgi.00436.2016⟩. ⟨hal-01630440⟩
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