MRC National Institute for Medical Research, London
Science for Health
Steve Ley group
Regulation of gene expression in immune responses by NF-κB and MAP kinases
Following infection, pathogenic microorganisms such as viruses and bacteria are initially recognised by specific receptors on the surface of neutrophils and macrophages. This triggers an immediate ‘innate’ immune response involving the production of proteins called chemokines and cytokines. These attract other immune cells to the sites of infection and also initiate the adaptive immune response that culminates in the production of protective antibodies and killing of infected cells.
Coordinating the expression of genes that control innate and adaptive immune responses involves activation of the NF-κB family of transcription factors and the ERK MAP kinase signalling enzyme. We study a signalling pathway that regulates both NF-κB and ERK MAP kinase activation by inducing proteolysis of the inhibitory protein NF-κB1 p105. We have recently found that p105 regulation of NF-κB is critical for the function of CD4 T cells during an immune response. Our current studies aim to determine whether blockade of p105 proteolysis might be useful for the treatment of specific autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.
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Regulation of NF-κB and ERK activation in innate immune responses.
Selected publications
- Kaiser, F; Cook, D; Papoutsopoulou, S; Rajsbaum, R; Wu, X; Yang, HT; Grant, S; Ricciardi-Castagnoli, P; Tsichlis, PN; Ley, SC and O'Garra, A (2009)
TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells.
Journal of Experimental Medicine 206, 1863-1871 PubMed abstract - Sriskantharajah, S; Belich, MP; Papoutsopoulou, S; Janzen, J; Tybulewicz, V; Seddon, B and Ley, SC (2009)
Proteolysis of NF-κB1 p105 is essential for T cell antigen receptor-induced proliferation.
Nature Immunology 10, 38-47 PubMed abstract - Papoutsopoulou, S; Symons, A; Tharmalingham, T; Belich, MP; Kaiser, F; Kioussis, D; O'Garra, A; Tybulewicz, V and Ley, SC (2006)
ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses.
Nature Immunology 7, 606-615 PubMed abstract
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