IL18 signaling promotes homing of mature Tregs into the thymus

Foxp3+ regulatory T cells (Tregs) are potent suppressor cells, essential for the maintenance of immune homeostasis. Most Tregs develop in the thymus and are then released into the immune periphery. However, some Tregs populate the thymus and constitute a major subset of yet poorly understood cells. Here we describe a subset of thymus recirculating IL18R+ Tregs with molecular characteristics highly reminiscent of tissue-resident effector Tregs. Moreover, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process. Finally, we demonstrate that IL18 signaling is critical for the induction of the key thymus-homing chemokine receptor - CCR6 on Tregs. Collectively, this study provides a detailed characterization of the mature Treg subsets in the mouse thymus and identifies a key role of IL18 signaling in controlling the CCR6-CCL20-dependent migration of Tregs into the thymus.Research in the Abramson laboratory is kindly supported by the European Research Council (ERC-2016-CoG-724821), Israel Science Foundation (1796/16), Sy Syms Foundation, Bill and Marika Glied and Family Fund, Wohl Biology Endowment Fund, Erica Drake Fund, The Enoch Foundation, Ruth and Samuel David Gameroff Family Foundation, and Lilly Fulop Fund for Multiple Sclerosis Research. CP was supported by Weizmann-La Caixa fellowship and Weizmann-Dean of faculty fellowship