Innate lymphoid cells at the human maternal-fetal interface in spontaneous preterm labor

Problem: Pathological inflammation is causally linked to preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Our aims were to investigate whether (i) the newly described family of innate lymphoid cells (ILCs) was present at the human maternal-fetal interface and (ii) ILC inflammatory subsets were associated with the pathological process of preterm labor. Methods of study: Decidual leukocytes were isolated from women with preterm or term labor as well as from gestational age-matched non-labor controls. ILCs (CD15(-)CD14(-)CD3(-)CD19(-)CD56(-)CD11b(-) CD127(+) cells) and their subsets (ILC1, T-bet+ ILCs; ILC2, GATA3+ ILCs; and ILC3, ROR gamma t+ ILCs) and cytokine expression were identified in the decidual tissues using immunophenotyping. Results: (i) The proportion of total ILCs was increased in the decidua parietalis of women with preterm labor; (ii) ILC1s were a minor subset of decidual ILCs during preterm and term gestations; (iii) ILC2s were the most abundant ILC subset in the decidua during preterm and term gestations; (iv) the proportion of ILC2s was increased in the decidua basalis of women with preterm labor; (v) the proportion of ILC3s was increased in the decidua parietalis of women with preterm labor; and (vi) during preterm labor, ILC3s had higher expression of IL-22, IL-17A, IL-13, and IFN-gamma compared to ILC2s in the decidua. Conclusion: ILC2s were the most abundant ILC subset at the human maternal-fetal interface during preterm and term gestations. Yet, during preterm labor, an increase in ILC2s and ILC3s was observed in the decidua basalis and decidua parietalis, respectively. These findings provide evidence demonstrating a role for ILCs at the maternal-fetal interface during the pathological process of preterm labor.