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A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression.

Abstract：

:Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor signaling pathways, was found to play a crucial part in controlling the maturation, cytokine production and immunostimulatory potency of dendritic cells (DCs). A20-silenced DCs showed spontaneous and enhanced expression of costimulatory molecules and proinflammatory cytokines and had different effects on T cell subsets: they inhibited T(reg) cells and hyperactivated tumor-infiltrating cytotoxic T lymphocytes and T helper cells that produced interleukin-6 and tumor necrosis factor-alpha and were refractory to T(reg) cell-mediated suppression. Hence, this study identifies A20 as an antigen presentation attenuator in control of antitumor immune responses during both the priming and the effector phases and provides a strategy to overcome T(reg) cell-mediated suppression in an antigen-specific manner, reducing the need to directly target T(reg) cells.

journal_name

Nat Med

journal_title

Nature medicine

authors

Song XT,Evel-Kabler K,Shen L,Rollins L,Huang XF,Chen SY

doi

10.1038/nm1721

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

258-65

issue

3

eissn

1078-8956

issn

1546-170X

pii

nm1721

journal_volume

14

pub_type

杂志文章

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