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RIP1-mediated regulation of lymphocyte survival and death responses

  • Current Immunology Research at Jefferson
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Abstract

RIP1 is an adaptor serine/threonine kinase associated with the signaling complex of death receptors (DRs) including Fas, TNFR1, and TRAIL-Rs which can initiate apoptosis. While DRs are dispensable throughout development, RIP1 deletion results in perinatal lethality. The developmental defect caused by absence of RIP1 remains unexplained. In previous studies, RIP1-deficient hematopoietic progenitors failed to reconstitute the T cell compartment and our recent data indicate a new role for RIP1 in TCR-induced activation of the pro-survival NF-κB pathway. Here, we show that RIP1 is also critical for B cell development. In addition, RIP1−/− B cells stimulated through LPS/TLR4 are impaired in NF-κB activation but have no major defect in the Akt pathway. Recently, RIP1 has also emerged as a critical player in necrosis-like death, necroptosis, in various cell lines. We have demonstrated that RIP1 deficiency can reverse the embryonic and T cell proliferation defects in mice lacking FADD, a caspase adaptor protein, which indicates a potential role for RIP1 in mediating in vivo necroptosis. We provide an overview and discussion of the accumulating data revealing insights into the diverse functions of RIP1 in survival and death signaling in lymphocytes.

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Acknowledgments

The authors thank Dr. M. Kelliher for providing the RIP1+/− mice, Erik Ronzone for technical help, Eric Zhang for critical reading of the manuscript, the Kimmel Cancer Center Flow Cytometry Facility and Jefferson Research Animal Facility for technical support. This study was supported in part by NIH grants (CA95454, AI083915, and AI076788), a TJU Enhancement grant to J.Z; and an NCI core grant (CA137494) to the Kimmel Cancer Center.

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  1. Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Jianke Zhang, Haibing Zhang, Stephen Rosenberg, Emily C. Zhang, Fengsong Qin & Mathew Farabaugh

  2. The Second Hospital of Jilin University, Changchun, China

    Jinghe Li

  3. Shanghai Public Health Center, Fudan University, Shanghai, China

    Xiaohui Zhou

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  1. Jianke Zhang
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Correspondence to Jianke Zhang.

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Zhang, J., Zhang, H., Li, J. et al. RIP1-mediated regulation of lymphocyte survival and death responses. Immunol Res 51, 227–236 (2011). https://doi.org/10.1007/s12026-011-8249-3

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