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.

个体发育早期的适当免疫细胞发育对于终生健康至关重要。常驻免疫细胞如何在新生儿阶段的屏障组织中建立以提供早期保护是一个重要但仍知之甚少的问题。我们在此报告，围产期皮肤归巢第 1 组先天淋巴细胞 (ILC1) 的发育程序优先生成有助于调节早期皮肤微生物群定植。我们发现皮肤归巢的 NK1.1 ⁺ ILC1 群体优先在小鼠围产期胸腺中产生。独特的胸腺环境和祖细胞负责在围产期优先生成皮肤归巢的 NK1.1 ⁺ ILC1。在皮肤中，NK1.1 ⁺ ILC1 调节适当的微生物群定植并控制新生小鼠中的机会性病原体铜绿假单胞菌。这些发现提供了对新生儿阶段组织特异性免疫细胞的发育和功能的深入了解，这是建立局部组织免疫稳态的关键时间窗口。