T cell PPARγ is required for the anti-inflammatory efficacy of abscisic acid against experimental IBD

The phytohormone abscisic acid (ABA) has been shown to be effective in ameliorating chronic and acute inflammation. The objective of this study was to investigate whether ABA's anti-inflammatory efficacy in the gut is dependent on peroxisome proliferator-activated receptor (gamma) over dot (PPAR gamma) in T cells. PPAR gamma-expressing and T cell-specific PPAR gamma null mice were fed diets with or without ABA (100 mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate. The severity of clinical disease was assessed daily, and mice were euthanized on Day 7 of the dextran sodium sulfate challenge. Colonic inflammation was assessed through macroscopic and histopathological examination of inflammatory lesions and real-time quantitative RT-PCR-based quantification of inflammatory genes. Flow cytometry was used to phenotypically characterize leukocyte populations in the blood and mesenteric lymph nodes. Colonic sections were stained immunohistochemically to determine the effect of ABA on colonic regulatory T (T(reg)) cells. ABA's beneficial effects on disease activity were completely abrogated in T cell-specific PPAR gamma null mice. Additionally. ABA improved colon histopathology, reduced blood F4/80(+)CD11b(+) monocytes, increased the percentage of CD4(+) T cells expressing the inhibitory molecule cytotoxic T lymphocyte antigen 4 in blood and enhanced the number of T(reg) cells in the mesenteric lymph nodes and colons of PPAR gamma-expressing but not T cell-specific PPAR gamma null mice. We conclude that dietary ABA ameliorates experimental inflammatory bowel disease by enhancing T(reg) cell accumulation in the colonic lamina propria through a PPAR gamma-dependent mechanism. (C) 2011 Elsevier Inc. All rights reserved.