Impact of the Adenosine Receptor A2BR Expressed on Myeloid Cells on Immune Regulation During Pregnancy

Authors

Stefanie Dietz
Janine Hebel
Jessica Rühle
Alisha Huff
Holger K Eltzschig
Trim Lajqi
Christian F Poets
Christian Gille
Natascha Köstlin-Gille

Language

English

Publication Date

12-1-2024

Journal

European Journal of Immunology

DOI

10.1002/eji.202451149

PMID

39460389

PMCID

PMC11628929

PubMedCentral® Posted Date

10-25-2024

PubMedCentral® Full Text Version

Post-print

Abstract

During pregnancy, the maternal immune system must carefully balance protection against pathogens with tolerance toward the semiallogeneic fetus. Dysfunctions of the immune system can lead to severe complications such as preeclampsia, fetal growth restriction, or pregnancy loss. Adenosine plays a role in physiological processes and plasma‐level increase during pregnancy. The adenosine receptor A2B (A2BR), which is expressed on both, immune and nonimmune cells, is activated by high adenosine concentrations, achieved during pregnancy. We investigated the impact of A2BR expressed on myeloid cells on immune regulation during pregnancy using a mouse model with myeloid deficiency for A2BR. We demonstrate systemic changes in myeloid and lymphoid cell populations during pregnancy in A2BR‐KO (Adora2B923f/f‐LysMCre) mice with increased monocytes, neutrophils, and T cells but decreased B cells as well as altered T‐cell subpopulations with decreased Th1 cells and Tregs and increased Th17 cells. Lack of A2BR on myeloid cells caused an increased systemic expression of IL‐6 but decreased systemic accumulation and function of MDSC and reduced numbers of uterine natural killer cells. The pregnancy outcome was only marginally affected. Our results demonstrate that A2BR on myeloid cells plays a role in immune regulation during pregnancy, but the clinical impact on pregnancy remains unclear.

Keywords

Animals, Female, Pregnancy, Mice, Receptor, Adenosine A2B, Myeloid Cells, Mice, Knockout, Killer Cells, Natural, Interleukin-6, Mice, Inbred C57BL, Myeloid A2BR knockout, Adenosine receptor, Immune regulation, Pregnancy

Published Open-Access

yes

Recommended Citation

Dietz, Stefanie; Hebel, Janine; Rühle, Jessica; et al., "Impact of the Adenosine Receptor A2BR Expressed on Myeloid Cells on Immune Regulation During Pregnancy" (2024). Faculty, Staff and Student Publications. 5606.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5606