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Exploring unconventional mechanisms of lymphoid tissue surveillance
Secondary Supervisor(s): Professor Sascha Ott
University of Registration: University of Warwick
BBSRC Research Themes:
Project Outline
Lymphoid tissues (bone marrow, thymus, spleen and lymph nodes) are specialized anatomical structures that orchestrate immune responses. In the steady state, immune cells continuously patrol these tissues via well-defined migratory routes, guided by chemokines and adhesion molecules. This dynamic surveillance ensures rapid detection of pathogens and maintenance of immune tolerance. Understanding immune surveillance within human lymphoid tissues is critical for elucidating how the immune system maintains homeostasis and responds to pathogens, cancerous cells, and tissue damage.
While conventional immune cells such as B cells and alpha beta (αβ) T cells have been extensively studied in these contexts, unconventional T cells, particularly human gamma delta (γδ) T cells, remain underexplored. In this project we seek to investigate the currently unknown contribution of human γδ T cells to lymphoid tissue surveillance, and in-turn explore novel mechanisms of immune regulation and tissue integrity.
The overall objective of the project will be to explore human γδ T cells that patrol lymphoid tissues and the novel mechanisms they use to contribute to lymphoid tissue homeostasis.
We will explore this objective via 3 inter-related aims:
1) Tissue-regulatory γδ T cells in primary (bone marrow) and secondary (spleen and lymph nodes) lymphoid tissues.
2) Tissue homing and segregation of lymphoid tissue γδ T cells.
3) γδ T cell receptor (TCR) mediated interactions with lymphoid tissue stromal cell niches.
To do this we'll combine established access to primary human tissues (blood, bone marrow and spleen) with cutting-edge immunological techniques, including high-dimensional spectral flow cytometry and single cell multiomics, that include γδ TCR information and spatial mapping of individual cells within the tissue architecture.