No abstract

Punicic acid (PUA) is a conjugated linolenic acid isomer that has shown promise in suppressing gut inflammation. The goal of this study is to elucidate the mechanisms by which PUA modulates mucosal immunity and prevents or ameliorates gut inflammation. The expression of peroxisome proliferator‐activated receptor (PPAR) α, γ and δ and their responsive genes was examined in the colonic mucosa of two mouse models of experimental inflammatory bowel disease (IBD). Immune cell‐specific PPAR γ null, PPAR δ null and wild‐type (WT) mice were administered control or PUA‐supplemented diets and challenged with 2.5% DSS. The phenotype of immune cell subsets was examined in the mucosal and peripheral immune system. The prophylactic efficacy of PUA was also examined in an IL‐10−/− model of IBD. PUA intake upregulated colonic PPAR δ, keratinocyte growth factor and the orphan nuclear receptor RORγt expression and suppressed colonic and M1 macrophage‐derived TNF‐α. In the mesenteric lymph nodes (i.e., mucosal inductive sites), PUA increased the levels of IL‐17 and IFN‐γ in CD8+ T cells. Clinically, PUA ameliorated DSS colitis in WT mice and spontaneous pan‐enteritis in IL‐10−/− mice. The loss of PPAR γ or δ impaired the preventive effects of PUA in IBD. Our studies provide molecular evidence in vivo suggesting that PUA modulates mucosal immune responses and ameliorates gut inflammation through PPAR γ and δ‐dependent mechanisms