Professor Kingston Mills

A major focus of my research is to examine the mechanisms of protective immunity against infectious pathogens, in particular to develop a better understanding of the factors that affect the induction, of the distinct subpopulations of CD4+ T cells, termed Th1, Th2 and T regulatory (Tr) and Th17 cells, and the role of the innate immune system, in particular dendritic cells, in directing T cell responses. The work has direct application to the development of new or improved vaccines and includes studies on Bordetella pertussis, diphtheria, influenza virus, HIV and hepatitis C virus.

In the last 5 years my group has been more focused on immune regulation and immune modulation by pathogens.

Figure 1 Immunity to Infection.

This has been made possible through a €6.5m Science Foundation Ireland award to examine the role of pathogen-derived molecules in modulating immune responses, with particular reference to the induction, regulation and function of T cell subtypes and the induction and control of inflammatory responses. Our hypothesis is that the study of immunomodulation by microbial pathogens is an ideal approach to understand mechanisms of protective immunity and immunoregulation in vivo and will allow the identification and characterization of novel immunomodulatory molecules with potential as therapies for immune mediated diseases. We have identified molecules capable of specifically suppressing or enhancing immune response that regulate or mediate certain human diseases. The application of this research is the development of new or improved vaccines against infectious diseases, active immunotherapeutics against cancer and anti-inflammatory therapeutics against autoimmune diseases. I have recently received a new SFI Investigator award (€3.6m) to study ‘the role of regulatory T cell control of pathogenic and effector T cells and their manipulation as potential therapies for human disease’.

Figure 2 Role of pathogenderived molecules in promoting the induction of regulatory T cells versus TH1 and TH2 cells.

The focus is still on the interface between innate and adaptive immunity, specifically how we can manipulate dendritic cells to selectively alter the balance of regulatory (Treg) versus effector (Th1 or Th2) or pathogenic (Th17). Our aim is to design new approaches to treat autoimmunity by enhancing induction of Treg which suppress Th17 cells and to develop new infectious diseases vaccines and cancer immunotherapeutics by enhancing induction of Th1 and Th2 cells, while inhibiting Treg cells.

Key Publications
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Suppression of antitumor immunity by IL-10 and TGF-ß-producing T cells infiltrating the growing tumor:
influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J Immunol 177 (2): 896-904, 2006.
Jarnicki, A.G., Lysaght, J, Todryk, S, Mills, K.H.G.

A crucial role for IL-1 in the induction of IL-17 producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203(7):1685-91.
(*denotes equal contribution), 2006.
Sutton, C, Keogh, B., Brereton, C., *Mills, K.H.G. and *Lavelle, E.C.

TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17- producing T cells.
J. Immunol. 177:7980-7989, 2006.
Higgins, S., Jarnicki, A, Lavelle, E.C. and Mills, K.H.G.

Bordetella pertussis adenylate cyclase toxin modulates innate and adaptive immune responses: distinct roles for acylation and enzymatic activity in immunomodulation and cell death. J. Immunol. 175: 730-738, 2005.
Boyd, A.P., Ross, P.J., Conroy, H., Mahon, N Lavelle, E.C.and Mills, K.H.G.

Regulatory T cells: friend or foe in immunity to infection. Nature Rev. Immunol. 4, 841-55, 2004.
Mills, K.H.G.

Last updated: May 9, 2008.

Trinity College Dublin

Professor Kingston Mills