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Trail-r Is A Negative Regulator Of Innate Immune Responses

*Abstract: The role of the TRAIL receptor (tumor necrosis factor-related apoptosis-inducing ligand, TRAIL-R, also known as Apo2L) in the induction of apoptosis of tumor cells is well established. However, the effect of TRAIL-R signaling on the innate immune system has not been well defined. TRAIL has been shown to be expressed on the surface of NK cells, T cells, Macrophages, and dendritic cells in an activation dependent manner. The inventor has found that signaling of the TRAIL-R inhibits the responsiveness of the innate immune system including the activity of dendritic cells and macrophages which play important roles in the resolution of infectious and chronic diseases.

The invention includes:

? Methods of modulating the innate immune response by inhibiting the TRAIL-R signaling process through administration of small molecules, antibodies, and certain genes.

? Methods of screening compounds including small molecules, antibodies, and genes for their effect in modulating the innate immune response through the inhibition of TRAIL-R signaling.

? An animal model is provided which has homozygous inactivation of the gene sequence encoding TRAIL-R which can be used for screening and research purposes.

Also see:
Diehl GE, Yue HH, Hsieh K, Kuang AA, Ho M, Morici LA, Lenz LL, Cado D, Riley LW, Winoto A. TRAIL-R as a negative regulator of innate immune cell responses. Immunity. 2004 Dec;21(6):877-89.

*Principal Investigation: Name: Gretchen Diehl
Department:

Name: Astar Winoto
Department:

Name: Herman Yue
Department:

附加資料: Patent Number: US7892539B2
Application Number: US200588459A
Inventor: Winoto, Astar | Diehl, Gretchen Elizabeth | Yue, Herman Heng
Priority Date: 24 Mar 2004
Priority Number: US7892539B2
Application Date: 23 Mar 2005
Publication Date: 22 Feb 2011
IPC Current: A61K003900 | A01K006700 | A61K003100 | A61K003817 | A61K0039395 | C07K0014705 | C12N001585 | C12Q000100 | G01N003353 | C07K001600 | C07K001622 | C07K001624 | C07K001628
US Class: 4241301 | 4350071 | 5140037 | 5303871 | 53038822 | 53038823 | 53038824 | 5303891 | 5303892 | 514002
Assignee Applicant: The Regents of the University of California
Title: Modulation of an innate immune response by altering TRIAL-R signaling
Usefulness: Modulation of an innate immune response by altering TRIAL-R signaling
Summary: The method is useful in modulating an innate immune response against infection or tumor.
Novelty: Modulating an innate immune response against infection by contacting cells associated with innate immune responses with an agent that alters tumor necrosis factor related apoptosis inducing ligand receptor (TRAIL-R) signaling

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