Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function.
CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases.
Peng
Guangyong
G
Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Guo
Zhong
Z
Kiniwa
Yukiko
Y
Voo
Kui Shin
KS
Peng
Weiyi
W
Fu
Tihui
T
Wang
Daniel Y
DY
Li
Yanchun
Y
Wang
Helen Y
HY
Wang
Rong-Fu
RF
D048868:Adaptor Proteins, Signal Transducing; D019264:Adoptive Transfer; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007108:Immune Tolerance; D053592:Interleukin-1 Receptor-Associated Kinases; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology; D011068:Poly G / Q000276:immunology; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C408982:CPG-oligonucleotide; D008024:Ligands; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D011068:Poly G; D017853:Phosphotransferases (Alcohol Group Acceptor); C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C507774:Irak4 protein, mouse