The role of T cell PPARgamma in mice with experimental inflammatory bowel disease

Guri, Amir J.; Mohapatra, Saroj K.; Horne, William T.; Hontecillas, Raquel; Bassaganya-Riera, Josep

The role of T cell PPARgamma in mice with experimental inflammatory bowel disease

dc.contributor.author	Guri, Amir J.	en
dc.contributor.author	Mohapatra, Saroj K.	en
dc.contributor.author	Horne, William T.	en
dc.contributor.author	Hontecillas, Raquel	en
dc.contributor.author	Bassaganya-Riera, Josep	en
dc.date.accessioned	2012-08-24T11:21:09Z	en
dc.date.available	2012-08-24T11:21:09Z	en
dc.date.issued	2010-06-10	en
dc.date.updated	2012-08-24T11:21:09Z	en
dc.description.abstract	Background Peroxisome proliferator-activated receptor Ω (PPAR Ω) is a nuclear receptor whose activation has been shown to modulate macrophage and T cell-mediated inflammation. The objective of this study was to investigate the mechanisms by which the deletion of PPAR Ω in T cells modulates immune cell distribution and colonic gene expression and the severity of experimental IBD. Methods PPAR Ω flfl; CD4 Cre+ (CD4cre) or Cre- (WT) mice were challenged with 2.5% dextran sodium sulfate in their drinking water for 0, 2, or 7 days. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to assess lymphocyte and macrophage populations in the blood, spleen, and mesenteric lymph nodes (MLN). Global gene expression in colonic mucosa was profiled using Affymetrix microarrays. Results The deficiency of PPAR Ω in T cells accelerated the onset of disease and body weight loss. Examination of colon histopathology revealed significantly greater epithelial erosion, leukocyte infiltration, and mucosal thickening in the CD4cre mice on day 7. CD4cre mice had more CD8+ T cells than WT mice and fewer CD4+FoxP3+ regulatory T cells (Treg) and IL10+CD4+ T cells in blood and MLN, respectively. Transcriptomic profiling revealed around 3000 genes being transcriptionally altered as a result of DSS challenge in CD4cre mice. These included up-regulated mRNA expression of adhesion molecules, proinflammatory cytokines interleukin-6 (IL-6) and IL-1β, and suppressor of cytokine signaling 3 (SOCS-3) on day 7. Gene set enrichment analysis (GSEA) showed that the ribosome and Krebs cycle pathways were downregulated while the apoptosis pathway was upregulated in colons of mice lacking PPAR Ω in T cells. Conclusions The expression of PPAR Ω in T cells is involved in preventing gut inflammation by regulating colonic expression of adhesion molecules and inflammatory mediators at later stages of disease while favoring the recruitment of Treg to the mucosal inductive sites.	en
dc.description.version	Published version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	BMC Gastroenterology. 2010 Jun 10;10(1):60	en
dc.identifier.doi	https://doi.org/10.1186/1471-230X-10-60	en
dc.identifier.uri	http://hdl.handle.net/10919/18837	en
dc.language.iso	en	en
dc.rights	Creative Commons Attribution 4.0 International	en
dc.rights.holder	Amir J Guri et al.; licensee BioMed Central Ltd.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.title	The role of T cell PPARgamma in mice with experimental inflammatory bowel disease	en
dc.title.serial	BMC Gastroenterology	en
dc.type	Article - Refereed	en
dc.type.dcmitype	Text	en