Flagellin stimulation suppresses IL-7 secretion of intestinal epithelial cells.
IL-7 is a cytokine, which regulates development, maintenance and proliferation of T lymphocytes within the human immune system. Production of IL-7 is observed in a sterile environment such as thymus or bone marrow. However, it is also known that intestinal epithelial cells (IECs) residing in close contact with numerous bacterial stimuli also produce IL-7. Here we show that secretion of IL-7 by IECs is significantly suppressed upon stimulation by various bacterial components, including flagellin. Analysis of the intracellular mechanism by which flagellin regulates IL-7 production revealed that flagellin down-regulates expression of the two major transcripts encoding IL-7. Surprisingly, such function of flagellin was independent from the known transcriptional regulation of the IL-7 gene, as no significant change was observed in the transcriptional activity regulated by the previously identified promoter region. As the stability of IL-7 mRNA also remained unchanged upon flagellin stimulation, results suggested the possible involvement of a yet unknown transcriptional regulation of the IL-7 gene. These results describe a novel regulation of IL-7 production by bacterial stimuli, presumably mediated via Toll-like receptors. The present system might contribute to regulate the local lymphocyte pool, in response to the gut luminal or sub-mucosal bacterial abundance.
Yoshioka
Atsushi
A
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Okamoto
Ryuichi
R
Oshima
Shigeru
S
Akiyama
Junko
J
Tsuchiya
Kiichiro
K
Nakamura
Tetsuya
T
Kanai
Takanori
T
Watanabe
Mamoru
M
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D015536:Down-Regulation; D005408:Flagellin / Q000494:pharmacology*; D006801:Humans; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism
C508605:IL7 protein, human; D015851:Interleukin-7; D012333:RNA, Messenger; D005408:Flagellin