title: SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis.
abstract: BACKGROUND
  SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-κB.
  
  
  METHODS
  A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility.
  
  
  RESULTS
  Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment.
  
  
  CONCLUSIONS
  These data confirm a protective role for SIRT2 against the development of inflammatory processes, pointing out a potential role for this sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory responses by increasing NF-κB acetylation and by reducing the M2-associated anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may be a potential approach for the treatment of inflammatory bowel disease.
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Giuseppe
authors: G
authors: Lo Sasso
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Keir Joe
authors: KJ
authors: Menzies
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Adrienne
authors: A
authors: Mottis
authors: Institute of Animal Pathology, University of Bern, Bern, Switzerland; School of Life Sciences, École Polytechnique Fédérale Lausanne, Lausanne, Switzerland.
authors: Alessandra
authors: A
authors: Piersigilli
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Alessia
authors: A
authors: Perino
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Department of Biomedical Informatics Division of Health Sciences, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
authors: Hiroyasu
authors: H
authors: Yamamoto
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Kristina
authors: K
authors: Schoonjans
authors: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Johan
authors: J
authors: Auwerx
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D037181:Lectins, C-Type / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D012720:Severity of Illness Index; D056565:Sirtuin 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D016264:Dextran Sulfate; D037181:Lectins, C-Type; D016328:NF-kappa B; D056565:Sirtuin 2; D000099192:CD69 Antigens; C418743:Sirt2 protein, mouse