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

Authors
  • Mendes, João1, 2, 3
  • Rodrigues-Santos, Paulo1, 2, 3, 3, 4
  • Areia, Ana Luísa1, 2, 5
  • Almeida, Jani-Sofia1, 2, 3, 3, 4
  • Alves, Vera1, 2, 3
  • Santos-Rosa, Manuel1, 2, 3
  • Mota-Pinto, Anabela1, 2, 3
  • 1 University of Coimbra, Polo III - Health Sciences Campus, Azinhaga Santa Comba, Celas, Coimbra, 3000-548, Portugal , Coimbra (Portugal)
  • 2 University of Coimbra, Apartado 9015, Coimbra, 3001-301, Portugal , Coimbra (Portugal)
  • 3 University of Coimbra, Rua Larga, Coimbra, 3004-504, Portugal , Coimbra (Portugal)
  • 4 University of Coimbra, Polo III - Health Sciences Campus Azinhaga Santa Comba, Celas, Coimbra, 3000-548, Portugal , Coimbra (Portugal)
  • 5 Coimbra Hospital and Universitary Centre (CHUC), Obstetrics Unit, R. Miguel Torga 1, Coimbra, 3030-165, Portugal , Coimbra (Portugal)
Type
Published Article
Journal
BMC Immunology
Publisher
Springer (Biomed Central Ltd.)
Publication Date
May 06, 2021
Volume
22
Issue
1
Identifiers
DOI: 10.1186/s12865-021-00423-x
Source
Springer Nature
Keywords
License
Green

Abstract

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.

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