Human peripheral blood monocytes and intestinal macrophage populations activate TGF-? via expression of the integrin ?v?8 and Investigating the effect of integrin ?v?8 on effector memory T cells.
| Dates: | 13 June 2016 |
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| Times: | 15:30 - 16:30 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Aoife Kelly, Stephanie Houston |
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Human peripheral blood monocytes and intestinal macrophage populations activate TGF-? via expression of the integrin ?v?8
Aoife Kelly
Transforming growth factor-beta (TGF?) plays a crucial role in regulation of immune responses. The cytokine is secreted as an inactive complex, with function tightly controlled at the level of its activation. Recent work has identified activators of TGF-? in mice, a major mechanism being via binding to ?v integrins. However, how TGF-? is activated to regulate human immune responses is poorly understood. Here, we show that human monocytes activate high levels of TGF-?, via expression of integrin ?v?8. When monocytes are differentiated to macrophages, high integrin ?v?8 expression and TGF-?-activating function is observed on tolerogenic versus inflammatory macrophages. Interestingly, we find ?v?8 expression on a human intestinal macrophage population expressing CD163 and CD206. This population is decreased in active Crohn’s disease. Thus, our data suggest expression of integrin ?v?8 on monocytes may play an important role in the induction and function of anti-inflammatory macrophages in the intestine via TGF-? activation.
Investigating the effect of integrin ?v?8 on effector memory T cells
Stephanie Houston
The adaptive immune response is characterised by the ability of lymphocytes to respond rapidly and effectively to previously encountered antigen. Protective memory is mediated by effector memory T cells (TEM) which migrate to inflamed tissues and display immediate effector function. Recently, we have identified a population of splenic CD4+ TEM that expresses the integrin avb8 in the steady state. Integrin avb8 plays an essential role in the activation of TGF-b, a cytokine that is fundamentally important in the maintenance of immune homoeostasis. Previous work has shown integrin avb8 is expressed by a subset of intestinal dendritic cells where it is crucial for the regulation of T cell responses. Additionally integrin avb8 expression is essential on Tregs where it acts to suppress T cell responses during active inflammation, via the activation of TGF-b. However, the function for integrin ?v?8 expression on TEM cells is completely unknown.
To determine the role of integrin avb8 expression on TEM in an inflammatory setting, we are performing a series of repeated infection experiments using mice specifically lacking expression of the integrin on T-cells. In this system, TEM lack functional b8, allowing us to determine the biological role of avb8 and TGF-b activation on TEM function.Additionally, we are currently determining important factors that regulate TEM formation and expression of integrin ?v?8, using germ-free animals to focus on the role of the microbiota. Together, our work will identify important novel pathways that regulate how memory T-cell responses are generated and controlled.
Speakers
Aoife Kelly
Role: Research Associate
Organisation: University of Manchester
Stephanie Houston
Role: Research Associate
Organisation: University of Manchester
Travel and Contact Information
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester
