IMMUNE TOLERANCE
The immune system is trained to recognize the difference between foreign invaders and the body’s own cells. While it will attack foreign entities, it will tolerate the presence of ‘self’. Our group is interested in the role of T lymphocytes in this immune tolerance, particularly in the context of pregnancy and skin immunity. Our research focuses on the balance between inflammatory Interleukin-17 (IL-17)-producing T cells and regulatory T cells (Tregs), and how the interplay between these cells makes or breaks tolerance.
Currently we are specifically interested in innate-like IL-17-producing T cells, particularly gamma/delta T cells. These cells are enriched at barrier sites, such as the skin, gut, lung and uterus/placenta, and are major players in the so-called ‘first line of defense’. However they can also be the culprits in autoimmune disease, inflammatory conditions and adverse pregnancy outcomes, highlighting the need for a greater understanding of the mechanisms that govern their behaviour.
Our research aims are three-fold. Firstly, to understand the mechanisms that can restrain their inflammatory behavior. Secondly, to determine how they are affected by a high fat diet in the context of pregnancy (particularly in the placenta) and in skin inflammation (psoriasis). Then thirdly, to unequivocally determine what role these IL-17-producing cells play in successful pregnancy.
Selected Publications
Pinget, G.V., T.M. Corpuz, J. Stolp, E.L. Lousberg, K.R. Diener, S.A. Robertson, J. Sprent, and K.E. Webster. 2016. The majority of murine gammadelta T cells at the maternal-fetal interface in pregnancy produce IL-17. Immunol. Cell Biol. doi:10.1038/icb.2016.48.
Corpuz, T.M., Stolp, J., Kim, H.O., Pinget, G.V., Gray, D.H., Cho, J.H., Sprent, J., and Webster, K.E. (2016). Differential Responsiveness of Innate-like IL-17- and IFN-gamma-Producing gammadelta T Cells to Homeostatic Cytokines. J. Immunol. 196, 645-654.
Webster, K.E., Kim, H.O., Kyparissoudis, K., Corpuz, T.M., Pinget, G.V., Uldrich, A.P., Brink, R., Belz, G.T., Cho, J.H., Godfrey, D.I., and Sprent, J. (2014). IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and survival. Mucosal immunology 7, 1058-1067.
Walters, S.N., Webster, K.E., Daley, S., and Grey, S.T. (2014). A role for intrathymic B cells in the generation of natural regulatory T cells. J. Immunol. 193, 170-176.
Loebbermann, J., H. Thornton, L. Durant, T. Sparwasser, K. E. Webster, J. Sprent, F. J. Culley, C. Johansson, and P. J. Openshaw. Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection. Mucosal immunology 2012; 5: 161-172.
McGuire, H. M., S. Walters, A. Vogelzang, C. M. Lee, K. E. Webster, J. Sprent, D. Christ, S. Grey, and C. King. Interleukin-21 is critically required in autoimmune and allogeneic responses to islet tissue in murine models. Diabetes 2011; 60: 867-875.
Walters, S., K. E. Webster, A. Sutherland, S. Gardam, J. Groom, D. Liuwantara, E. Marino, J. Thaxton, A. Weinberg, F. Mackay, R. Brink, J. Sprent, and S. T. Grey. Increased CD4+Foxp3+ T cells in BAFF-transgenic mice suppress T cell effector responses. J. Immunol. 2009; 182: 793-801.
Webster, K. E., S. Walters, R. E. Kohler, T. Mrkvan, O. Boyman, C. D. Surh, S. T. Grey, and J. Sprent. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J. Exp. Med. 2009; 206: 751-760.
More Garvan Publications
Staff in the Group
Research Assistant