The Tissue Treg project

Biggest paper yet from the lab now a preprint on BioRxiv. A massive open science resource on tissue Tregs, and what makes Tregs tick in the tissues.

This project started back when we thought that tissue Tregs formed by seeding tissues and differentiating into unique terminal cells. We had examples of fat Tregs and muscle Tregs becoming unique permanent residents, and wanted to look at Tregs across the tissues.

We undertook a massive project to look at Tregs across 48 different tissues. At first glance, tissue Tregs looked special. Take a tissue and compare it against lymphoid/blood Tregs and the differences are huge. But the more tissues you add, the more they look the same. The only three distinct phenotypes were gut, lymphoid and bulk non-lymphoid. (Try our interactive web-browser resource). They have the same phenotypes, they use the same genetic triggers to differentiate and they only stay in the tissues for around 3 weeks. In short, the "seeding & specialisation" model doesn't fit the data.

Instead we came up with the "pan tissue" model, where tissue Tregs slowly percolate between different tissues. We've spent years testing this model in every possible way. We used the TCR as genetic barcodes, showing that the same Treg #clones are found in different tissues. We used ProCode technology to make #retrogenics for the tissue Treg TCRs, formally demonstrating that they impart a multi-tissue Treg fate. We extracted cells from tissues and reintroduced them, showing that they are tissue-agnostic on rehoming. By every test, the "pan-tissue" model holds strong.

What is amazing is that tissue Tregs have so many key functions in tissue repair and homeostasis, and now we find that it is the same cells that are able to restore the balance across all of these different tissues. Tissue Tregs are global homeostatic police. They are regulatory cells with a pan-tissue beat. A truly amazing cell type.

Could only have happened due to an amazing team - lead by Oliver, Burton, Orian Bricard and James Dooley.