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Updated: Apr 26, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis
Giuseppe Lo Sasso1, Keir Joe Menzies1, Adrienne Mottis1
1Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
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.
Conclusion:
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.
Insights
SIRT2 plays a protective role in colitis by inhibiting inflammation. Sirt2 deficiency exacerbates inflammatory bowel disease by promoting NF-κB acetylation and reducing anti-inflammatory pathways.
Area of Science:
- Biochemistry
- Immunology
- Genetics
Background:
- Sirtuin 2 (SIRT2) is an NAD+-dependent deacylase involved in regulating inflammation.
- SIRT2 deacetylates and inhibits the p65 subunit of nuclear factor-kappa B (NF-κB).
Purpose of the Study:
- To investigate the role of SIRT2 in dextran sulfate sodium (DSS)-induced colitis.
- To determine the effect of Sirt2 deficiency on inflammatory responses in the gut.
Main Methods:
- Generated Sirt2 deficient (Sirt2-/-) mice using homologous recombination.
- Induced colitis in Sirt2-/- and wild-type (Sirt2+/+) littermate mice using DSS.
- Analyzed clinical and histological manifestations of colitis and macrophage polarization.
Main Results:
- Sirt2-/- mice exhibited more severe colitis than wild-type littermates.
- Sirt2 deficiency did not alter basal phenotype or intestinal morphology.
- Sirt2 deficiency promoted a pro-inflammatory environment by affecting macrophage polarization.
Conclusions:
- SIRT2 plays a protective role in colitis, acting as a suppressor of inflammatory processes.
- SIRT2 deletion exacerbates colitis by increasing NF-κB acetylation and reducing M2-associated anti-inflammatory pathways.
- SIRT2 activation may represent a therapeutic strategy for inflammatory bowel disease.
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