title: Exposure to fatty acids modulates interferon production by intraepithelial lymphocytes.
abstract: 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)-gamma 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-gamma in the supernatants were measured by ELISA, and the expression of IFN-gamma mRNA in IELs was determined by RT-PCR. Significant production of IFN-gamma from IELs was observed after anti-CD3 mAb stimulation. The combination of IL-12 and IL-18 induced significant levels of IFN-gamma production without TCR stimulation. Increased IFN-gamma mRNA was also observed after anti-CD3 or IL-12/IL-18 stimulation. Long-chain fatty acids dose-dependently inhibited the stimulated-IFN-gamma production at concentrations greater than 10 micro M, but the medium-chain fatty acid did not cause any significant changes in IFN-gamma production. IFN-gamma production from gammadelta IELs was very low compared with alphabeta 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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. miura@me.ndmc.ac.jp
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Hara
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Komoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Inamura
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Koseki
authors.forename: Chikako
authors.initials: C
authors.lastname: Watanabe
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hachimura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaminogawa
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D005227:Fatty Acids; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma