Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2019
Historique:
received: 11 02 2019
accepted: 16 05 2019
entrez: 6 7 2019
pubmed: 6 7 2019
medline: 23 10 2020
Statut: epublish

Résumé

Galectins are potent immunomodulators that regulate maternal immune responses in pregnancy and prevent the rejection of the semi-allogeneic fetus that also occurs in miscarriages. We previously identified a gene cluster on Chromosome 19 that expresses a subfamily of galectins, including galectin-13 (Gal-13) and galectin-14 (Gal-14), which emerged in anthropoid primates. These galectins are expressed only by the placenta and induce the apoptosis of activated T lymphocytes, possibly contributing to a shifted maternal immune balance in pregnancy. The placental expression of Gal-13 and Gal-14 is decreased in preeclampsia, a life-threatening obstetrical syndrome partly attributed to maternal anti-fetal rejection. This study is aimed at revealing the effects of Gal-13 and Gal-14 on T cell functions and comparing the expression of these galectins in placentas from healthy pregnancies and miscarriages. First-trimester placentas were collected from miscarriages and elective termination of pregnancies, tissue microarrays were constructed, and then the expression of Gal-13 and Gal-14 was analyzed by immunohistochemistry and immunoscoring. Recombinant Gal-13 and Gal-14 were expressed and purified, and their effects were investigated on primary peripheral blood T cells. The binding of Gal-13 and Gal-14 to T cells and the effects of these galectins on apoptosis, activation marker (CD25, CD71, CD95, HLA-DR) expression and cytokine (IL-1β, IL-6, IL-8, IL-10, IFNγ) production of T cells were examined by flow cytometry. Gal-13 and Gal-14 are primarily expressed by the syncytiotrophoblast at the maternal-fetal interface in the first trimester, and their placental expression is decreased in miscarriages compared to first-trimester controls. Recombinant Gal-13 and Gal-14 bind to T cells in a population- and activation-dependent manner. Gal-13 and Gal-14 induce apoptosis of Th and Tc cell populations, regardless of their activation status. Out of the investigated activation markers, Gal-14 decreases the cell surface expression of CD71, Gal-13 increases the expression of CD25, and both galectins increase the expression of CD95 on T cells. Non-activated T cells produce larger amounts of IL-8 in the presence of Gal-13 or Gal-14. In conclusion, these results show that Gal-13 and Gal-14 already provide an immunoprivileged environment at the maternal-fetal interface during early pregnancy, and their reduced expression is related to miscarriages.

Identifiants

pubmed: 31275299
doi: 10.3389/fimmu.2019.01240
pmc: PMC6593412
doi:

Substances chimiques

Biomarkers 0
Cytokines 0
Galectins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1240

Subventions

Organisme : NICHD NIH HHS
ID : HHSN275201300006C
Pays : United States

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Auteurs

Andrea Balogh (A)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Department of Immunology, Eotvos Lorand University, Budapest, Hungary.

Eszter Toth (E)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Roberto Romero (R)

Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD and Detroit, MI, United States.
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, United States.
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, United States.
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States.

Katalin Parej (K)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Structural Biophysics Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Diana Csala (D)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Nikolett L Szenasi (NL)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Istvan Hajdu (I)

Structural Biophysics Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Kata Juhasz (K)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Arpad F Kovacs (AF)

Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.

Hamutal Meiri (H)

TeleMarpe Ltd, Tel Aviv, Israel.

Petronella Hupuczi (P)

Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary.

Adi L Tarca (AL)

Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD and Detroit, MI, United States.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States.
Department of Computer Science, Wayne State University College of Engineering, Detroit, MI, United States.

Sonia S Hassan (SS)

Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD and Detroit, MI, United States.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, United States.

Offer Erez (O)

Division of Obstetrics and Gynecology, Maternity Department "D", Faculty of Health Sciences, Soroka University Medical Center, School of Medicine, Ben Gurion University of the Negev, Beer-Sheva, Israel.

Peter Zavodszky (P)

Structural Biophysics Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Janos Matko (J)

Department of Immunology, Eotvos Lorand University, Budapest, Hungary.

Zoltan Papp (Z)

Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary.
Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.

Simona W Rossi (SW)

Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland.

Sinuhe Hahn (S)

Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland.

Eva Pallinger (E)

Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.

Nandor Gabor Than (NG)

Systems Biology of Reproduction Momentum Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary.
First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.

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