IL-35-Producing Regulatory B Cells Are Positively Correlated with iTr35 Cells in Healthy Pregnancy with Altered Associations Following Pregnancy Loss
4 affiliations
- 1Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland
- 2Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland
- 3Gynaecology and Obstetrics Department, Antoni Falkiewicz Specialist Hospital, 52-114 Wrocław, Poland
- 4Healthcare Facility “Healthy Woman”, 54-034 Wrocław, Poland
Abstract
Immunological dysregulation may be involved in pregnancy loss. Regulatory T (Treg) and B (Breg) cells, together with interleukin-35 (IL-35), contribute to maternal-fetal tolerance. This study investigated peripheral regulatory cell populations in healthy pregnancy and recurrent spontaneous pregnancy loss (RPL), focusing on the potential relationships between regulatory B and T cells within a coordinated immunoregulatory network associated with immune tolerance during pregnancy. Peripheral blood samples were collected from healthy pregnant women and women following spontaneous miscarriage. Frequencies of Breg subsets, including B10 cells, immature B cells, and plasmablasts, as well as the proportions of cells expressing IL-35, IL-10, PD-L1, and PD-L2, were analyzed. Tregs and the regulatory T-cell subsets iTr35, Tr1, and Th3 were also examined for the expression of IL-35, IL-10, TGF-β, and PD-1. In addition, correlations between Treg and Breg populations were assessed. Miscarriage was associated with significantly reduced frequencies of IL-35+ immature B cells, IL-35+ B10-like cells, IL-35+ plasmablasts, IL-35+ Tregs, and iTr35 cells. A negative correlation was observed between PD-L1-expressing B10-like cells and the frequencies of Treg and Th3 cells. Notably, this study is the first to demonstrate a positive correlation between IL-35-producing Bregs and iTr35 cells in healthy pregnancy. These findings suggest that the observed relationships between peripheral regulatory B- and T-cell populations and IL-35-associated regulatory subsets may be relevant to immune regulation during pregnancy. The iTr35/IL-35+ Breg ratios showed potential discriminatory value between healthy pregnancy and pregnancy loss groups and may warrant further investigation as candidate markers in prospective studies.
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BibTeX
@article{slawek2026il35producing,
title = {{IL-35-Producing Regulatory B Cells Are Positively Correlated with iTr35 Cells in Healthy Pregnancy with Altered Associations Following Pregnancy Loss}},
author = {Anna Slawek and Paulina Kubik and Daria Lorek and Anna Ewa Kedzierska and Mateusz Spetany and Urszula Studzinska-Kalota and Anna Chelmonska-Soyta},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209207},
url = {https://www.mdpi.com/1422-0067/27/20/9207},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IL-35-Producing Regulatory B Cells Are Positively Correlated with iTr35 Cells in Healthy Pregnancy with Altered Associations Following Pregnancy Loss
AU - Anna Slawek
AU - Paulina Kubik
AU - Daria Lorek
AU - Anna Ewa Kedzierska
AU - Mateusz Spetany
AU - Urszula Studzinska-Kalota
AU - Anna Chelmonska-Soyta
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209207
UR - https://www.mdpi.com/1422-0067/27/20/9207
AB - Immunological dysregulation may be involved in pregnancy loss. Regulatory T (Treg) and B (Breg) cells, together with interleukin-35 (IL-35), contribute to maternal-fetal tolerance. This study investigated peripheral regulatory cell populations in healthy pregnancy and recurrent spontaneous pregnancy loss (RPL), focusing on the potential relationships between regulatory B and T cells within a coordinated immunoregulatory network associated with immune tolerance during pregnancy. Peripheral blood samples were collected from healthy pregnant women and women following spontaneous miscarriage. Frequencies of Breg subsets, including B10 cells, immature B cells, and plasmablasts, as well as the proportions of cells expressing IL-35, IL-10, PD-L1, and PD-L2, were analyzed. Tregs and the regulatory T-cell subsets iTr35, Tr1, and Th3 were also examined for the expression of IL-35, IL-10, TGF-β, and PD-1. In addition, correlations between Treg and Breg populations were assessed. Miscarriage was associated with significantly reduced frequencies of IL-35+ immature B cells, IL-35+ B10-like cells, IL-35+ plasmablasts, IL-35+ Tregs, and iTr35 cells. A negative correlation was observed between PD-L1-expressing B10-like cells and the frequencies of Treg and Th3 cells. Notably, this study is the first to demonstrate a positive correlation between IL-35-producing Bregs and iTr35 cells in healthy pregnancy. These findings suggest that the observed relationships between peripheral regulatory B- and T-cell populations and IL-35-associated regulatory subsets may be relevant to immune regulation during pregnancy. The iTr35/IL-35+ Breg ratios showed potential discriminatory value between healthy pregnancy and pregnancy loss groups and may warrant further investigation as candidate markers in prospective studies.
SN - 1422-0067
ER -