The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program
Oliver T. Burton, Orian Bricard, Samar Tareen, Václav Gergelits, Simon Andrews, Laura Biggins, Carlos P. Roca, Carly E. Whyte, Steffie Junius, Aleksandra Brajic, Emanuela Pasciuto, Magda Ali, Pierre Lemaître, Susan Schlenner, Harumichi Ishigame, Brian D. Brown, James Dooley, Adrian Liston
Abstract
regulatory T (Treg) cells in non-lymphoid tissues with unique characteristics compared with lymphoid Treg cells. However, tissue Treg cells have not been considered holistically across tissues. Here, we performed a systematic analysis of the Treg cell population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency, and common molecular dependencies. Tissue Treg cells from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg cell entry and were tissue-agnostic on tissue homing. Together, these results demonstrate that the tissue-resident Treg cell pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Treg cells, characterized by transient multi-tissue migration. This work suggests common regulatory mechanisms may allow pan-tissue Treg cells to safeguard homeostasis across the body.