isolation-characterization-dendritic-cells-macrophages-from-mouse

Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine

Within the intestine reside unique populations of innate and adaptive immune cells that are involved in promoting tolerance towards commensal flora and ...

Emory University

Dkk1 is a secreted antagonist of the Wnt/β-catenin signaling pathway. It is induced by inflammatory cytokines during colitis and exacerbates tissue damage by promoting apoptosis of epithelial cells. However, little is known about the physiologic role of Dkk1 in normal intestinal homeostasis and during wound repair following mucosal injury. We investigated whether inhibition of Dkk1 affects the morphology and function of the adult intestine.

The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair.

The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)-δ is highly expressed in colonic epithelial cells; however, the role of PPARδ ligands, such as fatty acids, in mucosal inflammation and malignant transformation has not been clarified. Recent evidence suggests that the anti-inflammatory/chemoprotective properties of fish oil (FO)-derived n-3 polyunsaturated fatty acids (PUFAs) may be partly mediated by PPARδ. Therefore, we assessed the role of PPARδ in modulating the effects of dietary n-3 PUFAs by targeted deletion of intestinal epithelial cell PPARδ (PPARδ(ΔIEpC)). Subsequently, we documented changes in colon tumorigenesis and the inflammatory microenvironment, i.e., local [mesenteric lymph node (MLN)] and systemic (spleen) T cell activation. Animals were fed chemopromotive [corn oil (CO)] or chemoprotective (FO) diets during the induction of chronic inflammation/carcinogenesis. Tumor incidence was similar in control and PPARδ(ΔIEpC) mice. FO reduced mucosal injury, tumor incidence, colonic STAT3 activation, and inflammatory cytokine gene expression, independent of PPARδ genotype. CD8(+) T cell recruitment into MLNs was suppressed in PPARδ(ΔIEpC) mice. Similarly, FO reduced CD8(+) T cell numbers in the MLN. Dietary FO independently modulated MLN CD4(+) T cell activation status by decreasing CD44 expression. CD11a expression by MLN CD4(+) T cells was downregulated in PPARδ(ΔIEpC) mice. Lastly, splenic CD62L expression was downregulated in PPARδ(ΔIEpC) CD4(+) and CD8(+) T cells. These data demonstrate that expression of intestinal epithelial cell PPARδ does not influence azoxymethane/dextran sodium sulfate-induced colon tumor incidence. Moreover, we provide new evidence that dietary n-3 PUFAs attenuate intestinal inflammation in an intestinal epithelial cell PPARδ-independent manner.

Article	Year
The Journal of nutrition\| PubMed ID: 16920860	2006
Cancer research\| PubMed ID: 18483285	2008
Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 18941214	2008
Prostaglandins, leukotrienes, and essential fatty acids\| PubMed ID: 18977126	2008
The Journal of nutrition\| PubMed ID: 19321585	2009
Prostaglandins, leukotrienes, and essential fatty acids\| PubMed ID: 19502020	2009
Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 19763480	2009
Immunology, endocrine & metabolic agents in medicinal chemistry\| PubMed ID: 19823600	2009
Progress in lipid research\| PubMed ID: 20176053	2010
Prostaglandins, leukotrienes, and essential fatty acids\| PubMed ID: 20188532	2010
The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair. Gastroenterology\| PubMed ID: 21440550	2011
Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARδ in inflammation-induced colon carcinogenesis. American journal of physiology. Gastrointestinal and liver physiology\| PubMed ID: 21940900	2012

Wooki Kim

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