Abstract Thymic 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 thymus ex vivo with 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 revealed in vivo thymic 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.

Type 1 immunity enables neonatal thymic ILC1 production