Decidual γδT cells of early human pregnancy produce angiogenic and immunomodulatory proteins while also possessing cytotoxic potential

Jasper Nörenberg; Péter Vida; Isabell Bösmeier; Barbara Forró; Anna Nörenberg; Ágnes Buda; Diana Simon; Szabina Erdő-Bonyár; Pál Jáksó; Kálmán Kovács; Éva Mikó; Tímea Berki; Emese Mezősi; Alíz Barakonyi

doi:10.3389/fimmu.2024.1382424

Decidual γδT cells of early human pregnancy produce angiogenic and immunomodulatory proteins while also possessing cytotoxic potential

Front Immunol. 2024 Mar 27:15:1382424. doi: 10.3389/fimmu.2024.1382424. eCollection 2024.

Authors

Jasper Nörenberg^{1

2

3}, Péter Vida³, Isabell Bösmeier¹, Barbara Forró⁴, Anna Nörenberg^{2

3

5}, Ágnes Buda³, Diana Simon^{2

6}, Szabina Erdő-Bonyár^{2

6}, Pál Jáksó⁴, Kálmán Kovács^{2

3}, Éva Mikó^{1

2

5}, Tímea Berki^{2

6}, Emese Mezősi^{2

7}, Alíz Barakonyi^{1

2

5}

Affiliations

¹ Department of Medical Microbiology and Immunology, University of Pécs Medical School, Clinical Center, Pécs, Hungary.
² National Laboratory on Human Reproduction, University of Pécs, Pécs, Hungary.
³ Department of Obstetrics and Gynaecology, University of Pécs Medical School, Clinical Center, Pécs, Hungary.
⁴ Department of Pathology, University of Pécs Medical School, Clinical Center, Pécs, Hungary.
⁵ Janos Szentagothai Research Centre, University of Pécs, Pécs, Hungary.
⁶ Department of Immunology and Biotechnology, University of Pécs Medical School, Clinical Center, Pécs, Hungary.
⁷ First Department of Internal Medicine, University of Pécs Medical School, Clinical Center, Pécs, Hungary.

Abstract

During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance. Furthermore, decidual γδT cells produce cytokines (G-CSF, FGF2) and cytotoxic mediators (Granulysin, IFN-γ), suggesting functions in placental growth and pathogen defense. However, these processes seem to be controlled by factors other than trophoblast-derived non-classical HLA molecules. These findings indicate that decidual γδT cells have the potential to actively contribute to the maintenance of healthy human pregnancy.

Keywords: HLA-E; HLA-G; NK receptors; angiogenic factors; cytokines; cytotoxic mediators; decidua; γδT cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents*
Cytokines / metabolism
Decidua
Female
HLA-G Antigens / genetics
HLA-G Antigens / metabolism
Humans
Placenta*
Pregnancy
Trophoblasts / metabolism

Substances

HLA-G Antigens
Cytokines
Antineoplastic Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. PTE ÁOK-KA grants funded this research (No: KA-2019-28, KA-2019-37), the Thematic Excellence Program 2020 - Institutional Excellence Sub-program of the Ministry for Innovation and Technology in Hungary, within the framework of the second thematic program of the University of Pécs and the European Union and co-financed by the European Social Fund: Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs (EFOP-3.6.1.-16-2016-00004). This work was supported by the National Research, Development and Innovation Fund of Hungary, financed under the TKP-2021-EGA-10 funding scheme. Further support was granted by the “National Laboratory on Human Reproduction”, project no. RRF-2.3.1-21-2022-00012, titled National Laboratory on Human Reproduction has been implemented with the support provided by the Recovery and Resilience Facility of the European Union within the framework of Programme Széchenyi Plan Plus.