Type 1 immunity enables neonatal thymic ILC1 production

Sci Adv. 2024 Jan 19;10(3):eadh5520. doi: 10.1126/sciadv.adh5520. Epub 2024 Jan 17.

Abstract

Acute thymic atrophy occurs following type 1 inflammatory conditions such as viral infection and sepsis, resulting in cell death and disruption of T cell development. However, the impact type 1 immunity has on thymic-resident innate lymphoid cells (ILCs) remains unclear. Single-cell RNA sequencing revealed neonatal thymic-resident type 1 ILCs (ILC1s) as a unique and immature subset compared to ILC1s in other primary lymphoid organs. Culturing murine neonatal thymic lobes with the type 1 cytokines interleukin-12 (IL-12) and IL-18 resulted in a rapid expansion and thymic egress of KLRG1+CXCR6+ cytotoxic ILC1s. Live imaging showed the subcapsular thymic localization and exit of ILC1s following IL-12 + IL-18 stimulation. Similarly, murine cytomegalovirus infection in neonates resulted in thymic atrophy and subcapsular localization of thymic-resident ILC1s. Neonatal thymic grafting revealed that type 1 inflammation enhances the homing of cytokine-producing thymus-derived ILC1s to the liver and peritoneal cavity. Together, we show that type 1 immunity promotes the expansion and peripheral homing of thymic-derived ILC1s.

MeSH terms

  • Animals
  • Atrophy
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate
  • Infant, Newborn
  • Interleukin-12
  • Interleukin-18*
  • Lymphocytes* / metabolism
  • Mice

Substances

  • Interleukin-18
  • Cytokines
  • Interleukin-12