Type 1 immunity enables neonatal thymic ILC1 production

Abstract

AbstractThymic atrophy occurs following type 1 inflammatory conditions like viral infection and sepsis, resulting in cell death and disruption of T-cell development. However, it remains undetermined whether the thymus actively contributes to the immune response. Thus, we cultured neonatal thymusex vivowith the type 1 cytokines IL-12 plus IL-18, resulting in a rapid shift from steady-state T-cell development to the production, expansion, and thymic exit of CXCR6+CD62L-type 1 innate lymphoid cells (ILC1s). Single-cell RNA-sequencing and functional assays identified these cells as embryonic-wave-derived KLRG1+ILC1s that mainly differentiated from immature neonatal thymic ILC1s. Confocal 3D imaging confirmed neonatal thymic ILC1 expansion during MCMV infection. Furthermore, thymic grafts revealedin vivothymic ILC1 egress and type 1 inflammation-induced homing of thymus-derived KLRG1+ILC1s to the liver and peritoneal cavity. Altogether, our data reveal a novel thymic function where type 1 immunity enables the production and peripheral homing of thymic-derived ILC1s.