Myeloid-T cell proximity is prominent in healthy pregnancies with extreme fetal-maternal HLA incompatibility

Author(s):
Tian, X.Z.; Krop, J.; Ijsselsteijn, M.E.; Kapsenberg, J.M.; Anholts, J.D.H.; Meeren, L. van der; Mei, H.L.; Huigen, M.H.J.; Keur, C. van der; Roelen, D.L. (0000-0002-1846-1193); Lashley, L.E.E.L.O.; Beelen, E. van; Koning, F.; Hoorn, M.L.P. van der; Eikmans, M. (0000-0002-9648-4227)
Published
2026
Publication type
Article / Letter to editor

Abstract

Pregnancy requires local immune tolerization. Oocyte donation (OD) pregnancies, with extensive fetal-maternal human leukocyte antigen (HLA) mismatching, are at higher risk of pre-eclampsia. We hypothesize that immune adaptations are needed at the fetal-maternal interface to maintain healthy pregnancy despite high HLA dissimilarity. By multispectral imaging, myeloid cells constituted 65% of the decidual immune cells and encompassed 12 distinct clusters. Fully-allogeneic healthy OD pregnancies displayed a higher frequency of CD163 +HLA-DR + myeloid cells and FoxP3 +CD4+ Tregs near CD4+ T cells compared to semi-allogeneic healthy pregnancies and pre-eclampsia, together with a Treg-reinforcing gene signature. Contrastingly, pre-eclampsia was characterized by enhanced inflammatory chemokine expression and oxidative-stress-gene imbalance. Pregnancy outcomes were unaffected by decidual pathology, maternal HLA antibodies, or fetal HLA-C/maternal KIR haplotypes. This study highlights the frequency, phenotypic diversity, and T cell proximity of decidual myeloid cells in OD pregnancies and suggests their immune regulatory effects to compensate for higher fetal-maternal HLA mismatch loads.

Date issued
2026-01-16
Language
English
Publisher
CELL PRESS
Is part of
iScience (2026), No. 1
hdl
1887/4298200
doi
10.1016/j.isci.2025.114179