We study the skin immune system with a particular focus on mechanisms that actively maintain immune cell tolerance in healthy skin.
At barrier sites such as the skin, gut and lung, mechanisms that promote immune tolerance are particularly important, and can regulate the threshold of inflammatory signals required to initiate an immune response. These tolerogenic mechanisms are required to prevent inappropriate immune cell activation in response to environmental stimuli such as commensal microbes or allergens. Dysregulation of these mechanisms can lead to inflammatory skin diseases such as psoriasis and atopic dermatitis, and targeting these pathways may represent novel therapeutic strategies for the treatment of such diseases.
We are investigating a number of pathways in skin that are known to be immune-regulatory at other tissue sites. One pathway that we have become particularly interested in involves signalling via the Ig superfamily members CD200 and CD200R1, and we have shown that this pathway is particularly important to maintain the appropriate activation threshold in skin immune cells.
We are also performing screens to uncover novel immune suppressive pathways that are dysregulated in inflammatory skin disease.
Recently, innate lymphoid cells (ILCs) have been implicated in psoriasis pathogenesis through their capacity to produce the cytokine IL-17. We are investigating pathways that regulate the activity of skin ILCs in healthy skin and may be perturbed in inflamed skin. These pathways may also be of importance to ILCs at other tissue sites.
Enquiries are welcomed from potential PhD students with a strong interest in immunology at barrier sites, a first class (or very high 2:1) degree in a biological discipline and with relevant laboratory experience.
Saunders, A. E., Shim, Y. A., Johnson, P. (2014). Innate Immune cell CD45 regulates lymphopenia-induced T cell proliferation. The Journal of Immunology. 193(6):2831-42.
Johnson, P., Samarakoon, A., Saunders, A. E., and Harder, K. W. (2012). CD45 (PTPRC). The Encyclopedia of Signaling Molecules, Springer. Choi, Sangdun (Ed.)
Bernhard, W., K. Barreto, A. Saunders, M. S. Dahabieh, P. Johnson, and I. Sadowski. (2011). The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response. FEBS letters 585:3549-3554.
Saunders, A. E., and P. Johnson. (2010). Modulation of immune cell signalling by the leukocyte common tyrosine phosphatase, CD45. Cellular signalling 22:339-348.
Saunders, A., Webb, L. M., Janas M. L., Hutchings, A., Pascall, J., Carter, C., Pugh, N., Morgan, G., Turner, M. and Butcher, G. W. (2010). Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes. Blood 115:3249-3257.
Wong, V. W. Y., Saunders A. E., Hutchings, A., Pascall, J. C., Carter, C., Bright, N. A., Walker, S. A., Ktistakis N. T., Butcher, G. W. (2010) The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein. Self/Nonself. 1:3.
Barnes, M. J., H. Aksoylar, P. Krebs, T. Bourdeau, C. N. Arnold, Y. Xia, K. Khovananth, I. Engel, S. Sovath, K. Lampe, E. Laws, A. Saunders, G. W. Butcher, M. Kronenberg, K. Steinbrecher, D. Hildeman, H. L. Grimes, B. Beutler, and K. Hoebe. (2010). Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5- deficient mice. The Journal of Immunology. 184:3743-3754.
Saunders, A., T. Lamb, J. Pascall, A. Hutchings, C. Dion, C. Carter, L. Hepburn, J. Langhorne, and G. W. Butcher. (2009). Expression of GIMAP1, a GTPase of the immunity-associated protein family, is not up-regulated in malaria. Malaria journal 8:53.