The intestinal environment, with its complex microbial communities and exogenous food antigens, represents a challenge for the immune system. The immune response needs to integrate the signals coming from microbiota and the tissue to strike the right balance between an inflammatory response to potential pathogens and tolerance to food antigens and beneficial microbiota. We investigate how the immune response is regulated at a local level and what is the role of epithelial cells in shaping the immune response.
Epithelial cells are at the frontline of the body’s defences against infections emanating from the intestine, and they send signals to instruct the immune system how to act. However, aberrant epithelial cells can misuse this system, for example during cancer, to prevent the immune system from eliminating tumors. We are researching the link between changes in epithelial cell behaviour and tolerance, focussing on some questions: How do pre-cancerous changes induce tolerance? Which immune cells are responsible for this tolerance? What is the role of these tolerance-inducing mechanisms in normal conditions of balance with the microbiota?
Meinicke, H., A. Bremser, M. Brack, P. Akeus, C. Pearson, S. Bullers, K. Hoffmeyer, M.P. Stemmler, M. Quiding-Jarbrink, and A. Izcue, Tumour-associated changes in intestinal epithelial cells cause local accumulation of KLRG1+ GATA3+ regulatory T cells in mice. Immunology, 2017. 152(1): p. 74-88.
Regulatory T cells prevent immune reactions by other immune cells in an antigen-specific manner to prevent misdirected immune responses. How the immunosuppressive potential of regulatory T cells is itself controlled is less well understood. We are researching how regulatory T cells numbers and activity are controlled in the organs to achieve tolerance to self and to innocuous antigens. We focus on the control of Foxp3+ T cells, which are key to establish and maintain tolerance in the gut.
Lupar, E., M. Brack, L. Garnier, S. Laffont, K.S. Rauch, K. Schachtrup, S.J. Arnold, J.C. Guery, and A. Izcue, Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction. J Immunol, 2015. 195(10): p. 4742-52.
Barnes, M.J., T. Griseri, A.M. Johnson, W. Young, F. Powrie, and A. Izcue, CTLA-4 promotes Foxp3 induction and regulatory T cell accumulation in the intestinal lamina propria. Mucosal Immunol, 2013. 6(2): p. 324-34.