Toll-Like Receptor 8-Mediated Reversal of CD4+ Regulatory T Cell Function

Guangyong Peng; Zhong Guo; Yukiko Kiniwa; Kui shin Voo; Weiyi Peng; Tihui Fu; Daniel Y. Wang; Yanchun Li; Helen Y. Wang; Rong-Fu Wang

doi:10.1126/science.1113401

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Abstract

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.

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Cells of the adaptive immune system that suppress potentially damaging immune responses unexpectedly are regulated by a receptor of the innate immune system.

Toll-Like Receptor 8-Mediated Reversal of CD4⁺ Regulatory T Cell Function

Abstract

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