Effects of n-3 PUFA on the CD4⁺ type 2 helper T-cell-mediated immune responses in Fat-1 mice.
It has been suggested that n-3 PUFA can be used as a preventive or therapeutic strategy to control allergic asthma. But little is known about the exact mechanisms by which n-3 PUFA modulates it. Here, the effects of elevated n-3 PUFA on ovalbumin (OVA) induced airway inflammation were investigated using Fat-1 transgenic mice that can convert n-6 PUFA to n-3 PUFA endogenously. First, we tested whether Fat-1 expression modulates CD4⁺ T-cell activation, proliferation, and differentiation in vitro and found that the Fat-1 expression attenuated all of these CD4⁺ T-cell responses by suppression of T-cell receptor mediated signaling and cytokine-mediated phosphorylation of STATs. When the Fat-1 mice were sensitized and challenged with the OVA, they showed a significant decrease in the recruitment of inflammatory cells into airway, the production of Th2 cytokines, eotaxin, and mucin in the lung, and the concentration of OVA-specific IgE in the serum. Furthermore, the differentiation of CD4⁺ T cells into Th2 was also decreased in the spleen of Fat-1 mice. Our results showed that an elevated level of n-3 PUFA was effective in preventing allergic airway inflammation by modulating the activation and differentiation of CD4⁺ T cells in Fat-1 mice.