International Journal of Molecular Sciences

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Research Advances in Reproductive Immunology

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Dr. Monika Kniotek

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Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Mazovian Voivodeship, Poland
Interests: pregnancy loss; reproduction; inflammation; immunocontraception; reproductive immunology

Special Issue Information

Dear Colleagues,

Reproductive immunology is a field that focuses on the study of how the immune system interacts with the reproductive system. Immunological disturbances at the feto-maternal interface can cause spontaneous abortions. Immunoregulation during pregnancy is a complex process involving tolerance of the maternal immune system to the embryo.

The main objective of this Special Issue focuses on how the immune system interacts with the reproductive system to influence fertility and the course of pregnancy.

The topics of this Special Issue include, but are not limited to, the following:

Reproductive immunology and pregnancy;
Maternal immune tolerance toward the fetus;
Pregnancy-related complications;
Maternal immune system.

This Special Issue aims to promote an in-depth understanding of the field of reproductive immunology. All reproductive diseases caused by immune system activity are included within the scope of this Special Issue. Since IJMS is a journal of molecular science, purely clinical studies are not suitable. However, clinical or pure model submissions with biomolecular experiments are welcome.

Dr. Monika Kniotek
Guest Editor

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22 pages, 2496 KiB

Open AccessArticle

Surface Immune Checkpoints as Potential Biomarkers in Physiological Pregnancy and Recurrent Pregnancy Loss

by Michał Zych, Monika Kniotek, Aleksander Roszczyk, Filip Dąbrowski, Robert Jędra and Radosław Zagożdżon

Int. J. Mol. Sci. 2024, 25(17), 9378; https://doi.org/10.3390/ijms25179378 - 29 Aug 2024

Viewed by 426

Abstract

Due to the genetic diversity between the mother and the fetus, heightened control over the immune system during pregnancy is crucial. Immunological parameters determined by clinicians in women with idiopathic recurrent spontaneous abortion (RSA) include the quantity and activity of Natural Killer (NK) and Natural Killer T (NKT) cells, the quantity of regulatory T lymphocytes, and the ratio of pro-inflammatory cytokines, which indicate imbalances in Th1 and Th2 cell response. The processes are controlled by immune checkpoint proteins (ICPs) expressed on the surface of immune cells. We aim to investigate differences in the expression of ICPs on T cells, T regulatory lymphocytes, NK cells, and NKT cells in peripheral blood samples collected from RSA women, pregnant women, and healthy multiparous women. We aim to discover new insights into the role of ICPs involved in recurrent pregnancy loss. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from blood samples obtained from 10 multiparous women, 20 pregnant women (11–14th week of pregnancy), and 20 RSA women, at maximum of 72 h after miscarriage. The PBMCs were stained for flow cytometry analysis. Standard flow cytometry immunophenotyping of PBMCs was performed using antibodies against classical lymphocyte markers, including CD3, CD4, CD8, CD56, CD25, and CD127. Additionally, ICPs were investigated using antibodies against Programmed Death Protein-1 (PD-1, CD279), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3, CD366), V-domain Ig suppressor of T cell activation (VISTA), T cell immunoglobulin and ITIM domain (TIGIT), and Lymphocyte activation gene 3 (LAG-3). We observed differences in the surface expression of ICPs in the analyzed subpopulations of lymphocytes between early pregnancy and RSA, after miscarriage, and in women. We noted diminished expression of PD-1 on T lymphocytes (p = 0.0046), T helper cells (CD3CD4 positive cells, p = 0.0165), T cytotoxic cells (CD3CD8 positive cells, p = 0.0046), T regulatory lymphocytes (CD3CD4CD25CD127 low positive cells, p = 0.0106), and NKT cells (CD3CD56/CD16 positive cells, p = 0.0438), as well as LAG-3 on lymphocytes T (p = 0.0225) T helper, p = 0.0426), T cytotoxic cells (p = 0.0458) and Treg (p = 0.0293), and cells from RSA women. Impaired expression of TIM-3 (p = 0.0226) and VISTA (p = 0.0039) on CD8 cytotoxic T and NK (TIM3 p = 0.0482; VISTA p = 0.0118) cells was shown, with an accompanying increased expression of TIGIT (p = 0.0211) on NKT cells. The changes in the expression of surface immune checkpoints indicate their involvement in the regulation of pregnancy. The data might be utilized to develop specific therapies for RSA women based on the modulation of ICP expression. Full article

(This article belongs to the Special Issue Research Advances in Reproductive Immunology)

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