Type 2 and type 3 innate lymphoid cells at the maternal-fetal interface: implications in preterm birth

BMC Immunology

Ana Luísa Areia¹  Vera Alves²  Manuel Santos-Rosa²  Paulo Rodrigues-Santos³  Jani-Sofia Almeida³  João Mendes⁴  Anabela Mota-Pinto⁴ 

[1] Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Polo III - Health Sciences Campus, Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal;Faculty of Medicine, Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Apartado 9015, 3001-301, Coimbra, Portugal;Coimbra Hospital and Universitary Centre (CHUC), Obstetrics Unit, R. Miguel Torga 1, 3030-165, Coimbra, Portugal;Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Polo III - Health Sciences Campus, Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal;Faculty of Medicine, Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Apartado 9015, 3001-301, Coimbra, Portugal;Faculty of Medicine (FMUC), Institute of Immunology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal;Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Polo III - Health Sciences Campus, Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal;Faculty of Medicine, Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Apartado 9015, 3001-301, Coimbra, Portugal;Faculty of Medicine (FMUC), Institute of Immunology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal;Center for Neuroscience and Cell Biology (CNC), Laboratory of Immunology and Oncology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal;Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Polo III - Health Sciences Campus Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal;Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Polo III - Health Sciences Campus, Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal;Faculty of Medicine, Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Apartado 9015, 3001-301, Coimbra, Portugal;General Pathology Institute, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal;

关键词: Preterm birth;    Inflammation;    Innate immune response;    Innate lymphoid cells;    Preterm labor;   

DOI  :  10.1186/s12865-021-00423-x

来源: Springer

【 摘 要 】

BackgroundPreterm birth (PTB) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The ability of innate lymphoid cells (ILCs) to act as pro-inflammatory mediators arose the interest to study their role in normal and pathological pregnancies.The aim of this work was to analyze the relative frequencies of ILCs subsets in pregnancy and the levels of IL-4, IL-17, IL-22, and IFN-γ as inflammatory mediators. Accordingly, we hypothesized that changes in the proportions of ILCs subpopulations could be related to preterm birth.MethodsWe analyzed 15 full-term delivery samples and six preterm delivery samples. In the full-term group (FTB) peripheral blood was taken during routine blood analysis, on 3 occasions: 1st, 2nd and 3rd trimester. After delivery, peripheral blood, cord blood and placenta were collected. In PTB group, peripheral blood samples were obtained on two occasions: before and 24 h after treatment with progesterone. We used flow cytometry to analyze ILCs in maternal peripheral blood, placenta, and cord blood samples. Maternal peripheral blood and cord blood samples were analyzed by enzyme-linked immunosorbent assay for IL-4, IL-17, IL-22, and IFN-γ plasma levels at the time of labor.ResultsWe observed significantly increased relative frequencies of ILC2 and ILC3 in the decidua, as well as an increase of ILC2 in cord blood samples in PTB group, compared to FTB samples. We also found a decrease in IFN-γ in peripheral blood samples of the PTB group, suggesting a functional withdrawal. Additionally, IL-4, IL-17, IL-22 levels were similar in PTB and FTB groups, denoting a relevant role in mediating labor.ConclusionOur results suggest that ILC2 and ILC3 play a role in PTB by mediating an inflammatory response. Further work is necessary to evaluate the importance of ILCs in the regulation of labor.

【 授权许可】

CC BY