IL-2 cytokine networks

If anyone is interested in our lab's work on IL-2 cytokine networks, I just gave a seminar on the topic, which I am putting up here:

It is a new talk for me, and was an interesting one to write. I started to work on IL-2 right at the start of my PhD. I was very keen to return to the topic when I opened my own lab in Belgium (2009), with one of my first PhD students (Dr Wim Pierson) working on the niche-sensing and niche-filling negative feedback loop that provides a stable number of Tregs in the system. (An excellent collaboration with one of my favourite immunologists, Prof Daniel Gray from WEHI, Australia).

Then Prof Stephanie Humblet-Baron joined my lab for a post-doc, wanting to work on a disease known as Familial hemophagocytic lymphohistiocytosis (FHL). At the time, this was thought to be a disease of CD8 hyper-activation and IFN-gamma. Thanks to great work by Stephanie, in mouse and human, we now know that FHL is only partly driven by IFN-gamma, and instead a key part of pathogenesis comes from flipping the negative feedback loop between IL-2 and Tregs into a postivie feedback loop between IL-2 and CD8 T cells.

Right back in 2009 we started to work on a new genetic switch that would let us turn IL-2 on in different cell types. At first I just wanted to see what would happen if Tregs could make their own IL-2. By breaking that dependency on exogenous IL-2 do you get a run-away Treg reaction? (answer: yes, yes you do). Once we finally made the mice, however, it just opened so many different doors. What happens if CD8 T cells make their own IL-2? How about NK cells, dendritic cells, B cells? What if we turn it on in different organs? It has really been a phenomenal mouse that just kept on delivering interesting results. Dr James Dooley led a team working on the mouse, and more recently Dr Carly Whyte drove the project to publication. Or, at least, pre-publication - you can see the paper here on BioRxiv. So many interesting aspects of IL-2 biology were illuminated by this work - easiest to show in a circuit diagram:

I hope you enjoy the seminar. Keep an ear out for the muffled bang at the 29 minute mark. It doesn't sound like much on the audio feed, but across Cambridge we all jumped up as the windows rattled and the building shuddered. I fumbled the graph on this slide, calling Tregs Tconv by mistake, wondering if an explosion had gone off downstairs. Fortunately it was just a sonic boom as fighter jets scrambled overhead.