Fatty acid-binding protein 5 limits the generation of Foxp3+ regulatory T cells through regulating plasmacytoid dendritic cell function in the tumor microenvironment

Shuhei Kobayashi, Tunyanat Wannakul, Kaname Sekino, Yu Takahashi, Yoshiteru Kagawa, Hirofumi Miyazaki, Banlanjo Abdulaziz Umaru, Shuhan Yang, Yui Yamamoto, Yuji Owada

Research output: Contribution to journalArticlepeer-review

Abstract

Plasmacytoid dendritic cells (pDCs) promote viral elimination by producing large amounts of Type I interferon. Recent studies have shown that pDCs regulate the pathogenesis of diverse inflammatory diseases, such as cancer. Fatty acid-binding protein 5 (FABP5) is a cellular chaperone of long-chain fatty acids that induce biological responses. Although the effects of FABP-mediated lipid metabolism are well studied in various immune cells, its role in pDCs remains unclear. This study, which compares wild-type and Fabp5−/− mice, provides the first evidence that FABP5-mediated lipid metabolism regulates the commitment of pDCs to inflammatory vs tolerogenic gene expression patterns in the tumor microenvironment and in response to toll-like receptor stimulation. Additionally, we demonstrated that FABP5 deficiency in pDCs affects the surrounding cellular environment, and that FABP5 expression in pDCs supports the appropriate generation of regulatory T cells (Tregs). Collectively, our findings reveal that pDC FABP5 acts as an important regulator of tumor immunity by controlling lipid metabolism.

Original languageEnglish
Pages (from-to)152-163
Number of pages12
JournalInternational Journal of Cancer
Volume150
Issue number1
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • FABP
  • Treg
  • pDC
  • translational research
  • tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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