Human Gene Set: GSE32034_UNTREATED_VS_ROSIGLIZATONE_TREATED_LY6C_HIGH_MONOCYTE_DN


Standard name GSE32034_UNTREATED_VS_ROSIGLIZATONE_TREATED_LY6C_HIGH_MONOCYTE_DN
Systematic name M9061
Brief description Genes down-regulated in Ly6C high monocytes: untreated versus rosiglitazone [PubChem=77999].
Full description or abstract PPAR? is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPAR? in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPAR?, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPAR? as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPAR? agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPAR? deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPAR?flox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPAR? sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22855714   Authors: Gautier EL,Chow A,Spanbroek R,Marcelin G,Greter M,Jakubzick C,Bogunovic M,Leboeuf M,van Rooijen N,Habenicht AJ,Merad M,Randolph GJ
Exact source GSE32034_3118_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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