Hofbauer cells (HBCs) are a population of immune cells in the human placenta that originate from the fetus. The publication describing the gene expression and gene expression regulation of these special cells is the result of several years of collaboration between the Department of Obstetrics and Gynecology at the University of Debrecen Clinical Center and the Nuclear Receptor Research Group at the Institute of Biochemistry and Molecular Biology (BMBI) at the University of Debrecen.
- Hofbauer cells became the focus of the work of our Nuclear Receptor research group first in the early 2000s. Unfortunately, that initiative ran into certain obstacles, because we were not able to isolate Hofbauer cells of high purity. Thus, we put the topic on “the back burner” at that time but, some twenty years later, the idea of experimenting with this special type of human cells resurfaced. It was then that we decided to restart the Hofbauer project in order to try and decipher the genetic and genomic processes that regulate the special functions of these cells. For a first step, Yale University researchers Seth Guller and Zhonghua Tang, with whom we have continued to maintain a very good professional relationship ever since and who are also co-authors of our article, provided us with the cell isolation protocol they had developed, so all we had to do was optimize it- said László Nagy, Professor at the Institute of Biochemistry and Molecular Biology at the University of Debrecen, to hirek.unideb.hu.
The project finally began during the spring of 2023 after preliminary planning, obtaining ethical approvals and ordering the reagents needed for isolation. The overall objective was to be the first to provide a detailed description of the gene expression and so-called epigenetic profile and protein-level heterogeneity of healthy human Hofbauer cells.
The research team was joined later by Ph.D. student Benjámin R. Baráth, who has been coordinating the theoretical and practical aspects of the study ever since. For the scientific part of the work, it was essential to involve a clinician who could help to develop and coordinate the clinical aspects of the research. The Head of our Obstetrics and Gynecology Clinic Tamás Deli has been a proactive and important participant in the scientific work from the outset, supported by the professional attitude of all the staff members of the clinic. Our research has also been complemented by experts from the Institute of Immunology (Márta Tóth) and the Szeged Biological Research Center (Gábor Szebeni and Patrícia Neuperger). The bioinformatic analysis and interpretation of the data obtained has been carried out under the leadership of Research Fellow Dóra Bojcsuk.
The research findings to date were published at the end of 2025 in JCI Insight, a highly ranked US-based journal focusing on clinical discovery research. This project is an outstanding example of effective cooperation between the scientific workshops and patient care units of the University of Debrecen, with significant results achieved even at the international level.
- In our article, we compared the gene expression and chromatin accessibility profiles of Hofbauer cells with those of other tissue-resident macrophages (which are a special population of immune cells). On the bases of this, we found genes that are characteristically highly and lowly expressed in Hofbauer cells, and based on this profile, functional characteristics of the cell type were also identified. According to our results, Hofbauer cells play an important part in placental vascularization, circulation regulation, intercellular structure formation and, perhaps most excitingly for us, placental lipid metabolism. The latter is supported by the fact that, based on our results, several nuclear receptors have a significant regulatory role in Hofbauer cells- said Benjámin R. Baráth, one of the co-first authors of the article.
So far, there have been as many as twenty-five placentas examined in the framework of the project. The research primarily involved expectant mothers who had undergone planned (elective) C-sections and had no obstetric complications. The researchers emphasize that these studies can serve as a valuable basis for future projects investigating the role of this cell type in pregnancy complications, which may in turn serve as points of departure for exploring new therapeutic approaches.
- Functioning as a regional center, our Obstetrics and Gynecology Clinic not only provides the placenta samples and the patient population necessary for the project, but we also have a comprehensive understanding of the clinical background of pregnancies, as the pathological cases are also treated by us. This is particularly valuable for a number of different reasons. In addition to normal pregnancies, quite a few conditions affecting the placenta, such as pregnancy toxemia (preeclampsia) or gestational diabetes, can also be included in the study. A key advantage we offer is predictability: scheduled caesarean sections allow us to time precisely both sampling and laboratory processing, so that the placenta can be examined immediately while it is still fresh. This is a significant competitive advantage even by international standards. The stable patient base, committed clinicians and a well-organized team of specialists together ensure a high-quality and reliable research environment,” said Zoárd Krasznai, Associate Professor and Director of the Department of Obstetrics and Gynecology at the University of Debrecen Clinical Center, and Tamás Deli, Head of the Perinatology Unit of the Department.
This recently published article is the result of just the first phase of the project. Currently, there are experiments also conducted in Debrecen on yet another cell type: trophoblasts. In addition, a series of experiments investigating the interaction between Hofbauer cells and trophoblasts has been underway for more than twelve months as part of an American collaboration at the St. Petersburg, Florida, campus of Johns Hopkins University.
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