Journal
JOURNAL OF IMMUNOLOGY
Volume 205, Issue 4, Pages 1113-1124Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2000184
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Funding
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [R01 AI121250-A1, T32 AI 118684]
- National Institute of General Medical Sciences, NIH [T32 GM 008216]
- American Academy of Pediatrics Section on Neonatal-Perinatal Medicine Marshall Klaus Award
- Children's Hospital of Philadelphia Research Institute Foerderer Award
- Division of Neonatology of the Children's Hospital of Philadelphia
- University of Pennsylvania University Research Foundation
- March of Dimes Foundation Prematurity Research Center at the University of Pennsylvania
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Disruption in homeostasis of IL-15 is linked to poor maternal and fetal outcomes during pregnancy. The only cells described to respond to IL-15 at the early maternal-fetal interface have been NK cells. We now show a novel population of macrophages, evident in several organs but enriched in the uterus of mice and humans, expressing the beta-chain of the IL-15R complex (CD122) and responding to IL-15. CD122(+) macrophages (CD122+Macs) are morphologic, phenotypic, and transcriptomic macrophages that can derive from bone marrow monocytes. CD122+Macs develop in the uterus and placenta with kinetics that mirror IFN activity at the maternal-fetal interface. M-CSF permits macrophages to express CD122, and IFNs are sufficient to drive expression of CD122 on macrophages. Neither type I nor type II IFNs are required to generate CD122+Macs, however. In response to IL-15, CD122+Macs activate the ERK signaling cascade and enhance production of proinflammatory cytokines after stimulation with the TLR9 agonist CpG. Finally, we provide evidence of human cells that phenocopy murine CD122+Macs in secretory phase endometrium during the implantation window and in first-trimester uterine decidua. Our data support a model wherein IFNs local to the maternal-fetal interface direct novel IL-15-responsive macrophages with the potential to mediate IL-15 signals critical for optimal outcomes of pregnancy.
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