Preferential Perinatal Development of Skin-Homing NK1.1⁺ Innate Lymphoid Cells for Regulation of Cutaneous Microbiota Colonization

Highlights

• Perinatal thymi support preferential generation of skin-homing CCR10+ NK1.1+ ILC1s

• PLZF is crucial for the perinatal thymic development of CCR10+ NK1.1+ ILC1s

• Perinatally derived NK1.1+ ILC1s contribute to skin immune system until adulthood

• NK1.1+ ILC1s control skin commensal bacterial colonization during neonatal stages

Summary

Proper immune cell development at early ontogenic stages is critical for life-long health. How resident immune cells are established in barrier tissues at neonatal stages to provide early protection is an important but still poorly understood question. We herein report that a developmentally programmed preferential generation of skin-homing group 1 innate lymphoid cells (ILC1s) at perinatal stages helps regulate early skin microbiota colonization. We found that a population of skin-homing NK1.1⁺ ILC1s was preferentially generated in the perinatal thymi of mice. Unique thymic environments and progenitor cells are responsible for the preferential generation of skin-homing NK1.1⁺ ILC1s at perinatal stages. In the skin, NK1.1⁺ ILC1s regulate proper microbiota colonization and control the opportunistic pathogen Pseudomonas aeruginosa in neonatal mice. These findings provide insight into the development and function of tissue-specific immune cells at neonatal stages, a critical temporal window for establishment of local tissue immune homeostasis.