Fatty acid-binding protein 5 limits the generation of Foxp3+ regulatory T cells through regulating plasmacytoid dendritic cell function in the tumor microenvironment.
Shuhei KobayashiTunyanat WannakulKaname SekinoYu TakahashiYoshiteru KagawaHirofumi MiyazakiBanlanjo Abdulaziz UmaruShuhan YangYui YamamotoYuji OwadaPublished in: International journal of cancer (2021)
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.
Keyphrases
- dendritic cells
- binding protein
- regulatory t cells
- fatty acid
- immune response
- toll like receptor
- gene expression
- wild type
- nuclear factor
- oxidative stress
- type diabetes
- inflammatory response
- adipose tissue
- sars cov
- poor prognosis
- skeletal muscle
- genome wide
- young adults
- heat stress
- high fat diet induced
- replacement therapy
- lymph node metastasis