IFNs Drive Development of Novel IL-15-Responsive Macrophages.
Scott M Gordon1,2, Mailyn A Nishiguchi2, Julie M Chase3
1Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Journal of Immunology (Baltimore, Md. : 1950)
|July 22, 2020
Summary
Researchers discovered novel IL-15-responsive macrophages (CD122+Macs) in the uterus. These cells, influenced by interferons (IFNs), may play a critical role in mediating IL-15 signals for successful pregnancy outcomes.
Area of Science:
- Immunology
- Reproductive Biology
- Cell Biology
Background:
- Interleukin-15 (IL-15) homeostasis disruption is linked to adverse pregnancy outcomes.
- Natural Killer (NK) cells were the only known IL-15 responders at the maternal-fetal interface.
Purpose of the Study:
- To identify novel IL-15-responsive cells at the maternal-fetal interface.
- To characterize the role of these cells in pregnancy.
Main Methods:
- Identification and characterization of CD122+ macrophages (CD122+Macs) in mice and humans.
- Analysis of CD122 expression regulation by M-CSF and interferons (IFNs).
- Assessment of CD122+Macs response to IL-15 and TLR9 agonist CpG.
Main Results:
- A novel population of CD122+Macs was identified in the uterus and placenta, originating from bone marrow monocytes.
- CD122 expression on macrophages is regulated by M-CSF and IFNs.
- CD122+Macs activate ERK signaling and enhance pro-inflammatory cytokine production upon IL-15 and CpG stimulation.
- Human cells phenocopying murine CD122+Macs were found in the endometrium and decidua.
Conclusions:
- Interferons at the maternal-fetal interface may direct novel IL-15-responsive macrophages.
- These CD122+Macs have the potential to mediate crucial IL-15 signals for optimal pregnancy.
- This discovery offers new insights into the immune mechanisms governing successful pregnancy.
