Professor of Immunology
T lymphocyte homeostasis and function.
T lymphocytes are immune cells that play a central role in regulating immune responses. There are several T cell types, all with different functions, so having the right number and composition of these cells is essential for a normal immunity to infection.
The focus of my group is on understanding the molecular and cellular mechanisms that regulate development and maintenance of mature T cells. We have a particular interested in how developing T cells become fully functional and the mechanisms controlling survival and proliferation once full maturity has been attained.
We use mouse genetics to dissect the signalling pathways and molecular mechanisms regulating T cell development and homeostasis. Currently we are focused in the role of NF-kB signalling, as we have identified a key role for this family of transcription factors for the normal development of T cells. Additionally, we have identified a novel signalling pathway controlling cell death downstream of TNF signalling in T cells. The inhibitor of kappa B kinase complex (IKK) is an essential trigger for NF-kB activity downstream of TNF receptor signalling. We have recently shown that the IKK complex also promotes the survival of T cells in the face of TNF stimulation by directly repressing activity of a key death inducing kinase, RIPK1. Surprisingly, this function does not depend on NF-kB activation. Our future work is focused upon understanding how this pathway is regulated and controls normal T cell function in health and disease.
To gain systems level understanding of complex cellular behaviours of the immune system, we have recently established a temporal fate mapping method that allows us to visualise and investigate the processes underlying tonic reconstitution of the immune system throughout the life course of a host. Employing mathematical analysis is key to understanding and interpreting the data from these experiments. We develop mathematical models of key immunological processes that test our understanding, provide novel insights into systems function and generate new hypotheses that can in turn be tested in the laboratory.
- Selected publications
From last five years:
- Webb LV, Barbarulo A, Huysentruyt J, Vanden Berghe T, Takahashi N, Ley S, Vandenabeele P, Seddon B. Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB. Immunity. 2019 Feb 19;50(2):348-361.e4
- Rane S, Hogan T, Seddon B, Yates AJ. Age is not just a number: Naive T cells increase their ability to persist in the circulation over time. PLoS Biol. 2018 Apr 11;16(4):e2003949
- Yang J, Cornelissen F, Papazian N, Reijmers RM, Llorian M, Cupedo T, Coles M, Seddon B. IL-7-dependent maintenance of ILC3s is required for normal entry of lymphocytes into lymph nodes. J Exp Med. 2018 Apr 2;215(4):1069-1077
- Gossel G, Hogan T, Cownden D, Seddon B, Yates AJ. Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels. Elife. 2017 Mar 10;6. pii: e23013
- Webb LV, Ley SC, Seddon B. TNF activation of NF-κB is essential for development of single-positive thymocytes. J Exp Med. 2016 Jul 25;213(8):1399-407
- Hogan T, Gossel G, Yates AJ, Seddon B. Temporal fate mapping reveals age-linked heterogeneity in naive T lymphocytes in mice. Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):E6917-26. doi: 10.1073/pnas.1517246112
- Silva A, Cornish G, Ley SC, Seddon B. NF-κB signaling mediates homeostatic maturation of new T cells. Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):E846-55.
- View all publications
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