title: Th17 cell accumulation is decreased during chronic experimental colitis by (n-3) PUFA in Fat-1 mice.
abstract: During colon inflammation, Th17 cells and immunosuppressive regulatory T cells (Treg) are thought to play promotive and preventative roles, respectively. Dietary (n-3) PUFA favorably modulate intestinal inflammation in part by downregulating T-cell activation and functionality. We used the Fat-1 mouse, a genetic model that synthesizes long-chain (n-3) PUFA de novo, to test the hypothesis that (n-3) PUFA protect against colonic inflammation by modulating the polarization of Treg and Th17 cells during colitis. Male and female wild-type (WT) and Fat-1 mice were administered dextran sodium sulfate (DSS) in the drinking water (2.5%) to induce acute (5 d DSS) or chronic (3 cycles DSS) colitis and the percentage of Treg and Th17 cells residing locally [colonic lamina propria (cLP)] and systemically (spleen) was determined by flow cytometry. The percentage of Treg in either tissue site was unaffected by genotype (P > 0.05); however, during chronic colitis, the percentage of Th17 cells residing in both the spleen and cLP was lower in Fat-1 mice compared to WT mice (P < 0.05). Colonic mucosal mRNA expression of critical Th17 cell cytokines and chemokine receptors (IL-17F, IL-21, and CCR6) were lower, whereas expression of the Th17 cell suppressive cytokine, IL-27, was greater in Fat-1 mice compared to WT mice during chronic colitis (P < 0.05). Moreover, colon histological scores were improved in Fat-1 mice (P < 0.05). Collectively, these results demonstrate for the first time, to our knowledge, that (n-3) PUFA can modulate the colonic mucosal microenvironment to suppress Th17 cell accumulation and inflammatory damage following the induction of chronic colitis.
authors: Program in Integrative Nutrition and Complex Diseases, Texas A&M University System Health Science Center, Texas A&M University, College Station, TX, USA.
authors: Jennifer M
authors: JM
authors: Monk
authors: Qian
authors: Q
authors: Jia
authors: Evelyn
authors: E
authors: Callaway
authors: Brad
authors: B
authors: Weeks
authors: Robert C
authors: RC
authors: Alaniz
authors: David N
authors: DN
authors: McMurray
authors: Robert S
authors: RS
authors: Chapkin
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3