Differential modulation in the functions of intestinal dendritic cells by long- and medium-chain fatty acids.
BACKGROUND
Although dendritic cells (DCs) play significant roles in intestinal immune responses, little is known regarding the direct effects of luminal foods on DC functions in the intestinal mucosa. In this study, we examined the effects of fatty acids (FAs) with various chain length on the phagocytic function, antigen presentation, and chemotaxis of intestinal DCs.


METHODS
DCs obtained from the thoracic duct lymph of mesenteric lymphadenectomized rats were cultured with long [arachidonic acid (AA) or oleic acid] or medium (octanoic acid) chain FAs with interleukin-4 and granulocyte macrophage-colony stimulating factor. Tumor necrosis factor-alpha was added in the maturation group. Phagocytic function was examined by the intake of fluorescent microbeads. The expression of cell surface molecules was determined by immunocytochemistry or fluorescence-activated cell sorting (FACS). Antigen presentation ability was evaluated by coincubating keyhole limpet hemocyanin (KLH)-sensitized spleen lymphocytes and KLH-pulsed DCs. Migratory ability of DCs toward the chemokines CC chemokine ligand (CCL) 20 and CCL21 was also assessed.


RESULTS
There was a maturation-induced decrease in phagocytic function, and an increased expression of major histocompatibility complex (MHC) class II molecules. Exposure of DCs to both long- and medium-chain FAs maintained phagocytic ability. The expression of MHC class II molecules was significantly suppressed only by long-chain FAs. The expression of costimulatory factors was suppressed only by AA. Long- but not medium-chain FAs suppressed the antigen presentation ability of DCs induced by maturation. Chemotactic ability of mature DCs toward CCL21 was abrogated only by long-chain FAs.


CONCLUSIONS
The data suggest that intraluminal exposure to long- and medium-chain FAs may differentially modulate the immune functions of intestinal DCs.
Tsuzuki
Yoshikazu
Y
Second Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.
Miyazaki
Jyunichi
J
Matsuzaki
Koji
K
Okada
Yoshikiyo
Y
Hokari
Ryota
R
Kawaguchi
Atsushi
A
Nagao
Shigeaki
S
Itoh
Kazuro
K
Miura
Soichiro
S
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002469:Cell Separation; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D019742:Chemokines, CC; D005227:Fatty Acids; D000949:Histocompatibility Antigens Class II