Immune Regulation, Autoimmune Disease and Infection

We aim to discover how genetically determined variation in immune regulation balances the risks of autoimmune disease and infection. Regulation of the B cell immune response is a major interest. We have investigated the function of inhibitory receptors such as FcyRIIb, which act as “brakes” on the immune system. We have shown that even subtle changes in expression of FcyRIIb on B cells can prevent or induce SLE in mice. Natural polymorphisms in FcyRIIb are associated with immune dysregulation (see Figure) and autoimmune diseases such as systemic lupus erythematosus (SLE) in both mouse and man. Some reduce function and are common in Asia and Africa, where malaria is endemic.

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Selected References

McKinney EF, Lee, JC, Jayne DRW, Lyons PA and Smith KGC (2015). T cell exhaustion, costimulation and clinical outcome in autoimmunity and infection. Nature, in press.

Linterman, MA, Denton, AE, Divekar, DP, Zvetkova, I, Kane, L, Ferreira, C, Veldhoen, M, Clare, S, Dougan G, Espéli, M, and Smith, KGC (2014). CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection. ELIFE, 3. doi:10.7554/eLife.03180

Wallin , EF, Jolly, EC, Suchánek, O, Bradley, JA, Espéli, M, Jayne, DRW, Linterman, MA, and Smith, KGC (2014). Human T follicular helper and T follicular regulatory cell maintenance is independent of germinal centers. Blood, 124(17), 2666-74. doi:10.1182/blood-2014-07-585976

Richard, AC, Lyons, PA, Peters, JE, Biasci, D, Flint, SM, Lee, JC, and Smith, KGC (2014). Comparison of gene expression microarray data with count-based RNA measurements informs microarray interpretation. BMC Genomics, 15, 649. doi:10.1186/1471-2164-15-649

Lee, JC, Espéli, M, Anderson, CA, Linterman, MA, Pocock, JM, Williams, NJ, et al, and Smith, KGC (2013). Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell, 155(1), 57-69. doi:10.1016/j.cell.2013.08.034

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