Trail-r Is A Negative Regulator Of Innate Immune Responses

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. Javed Afzal jafzal@berkeley.edu 510-643-7201

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