Exposure to fatty acids modulates interferon production by intraepithelial lymphocytes

Intraepithelial lymphocytes (IELs) play important roles in intestinal mucosal immunity. Although fatty acids are known to modulate the functions of immune effector cells, there has been no information about how fat exposure affects immunological function of IELs. In this study, we examined how fatty acids of various chain lengths modulate the production of interferon (IFN)-γ by IELs stimulated with T-cell receptor (TCR) or interleukin (IL)-12/IL-18. IELs isolated from the small intestine of BALB/c mice were stimulated with plate-coated anti-CD3 monoclonal antibody (mAb) or IL-12/IL-18. They were coincubated in microtiter plates for 3 days with various concentrations of fatty acid micelles. We used arachidonic acid, linoleic acid, and oleic acid as long-chain fatty acids, and used octanoic acid as a medium-chain fatty acid. IFN-γ in the supernatants were measured by ELISA, and the expression of IFN-γ mRNA in IELs was determined by RT-PCR. Significant production of IFN-γ from IELs was observed after anti-CD3 mAb stimulation. The combination of IL-12 and IL-18 induced significant levels of IFN-γ production without TCR stimulation. Increased IFN-γ mRNA was also observed after anti-CD3 or IL-12/IL-18 stimulation. Long-chain fatty acids dose-dependently inhibited the stimulated-IFN-γ production at concentrations greater than 10 μM, but the medium-chain fatty acid did not cause any significant changes in IFN-γ production. IFN-γ production from γδ IELs was very low compared with αβ IELs, however, both populations showed similar attenuating patterns when treated with long-chain fatty acids. There is a possibility that the exposure of IELs to intraluminal fatty acids significantly modifies the immune function of intestinal mucosa. [Copyright &y& Elsevier]