Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy.
BACKGROUND
Immunoregulation implies the activation of negative pathways leading to the modulation of specific immune responses. Co-inhibitory receptors (such as PD-1 and TIM-3) represent possible tools for this purpose. PD-1 and TIM-3 have been demonstrated to be present on immune cells suggesting general involvement in immunosuppression such as fetomaternal tolerance. The aim of our study was to investigate the expression pattern of PD-1, TIM-3, and its ligand Gal-9 on different immune cell subsets in the peripheral blood and at the fetomaternal interface in pregnant mice.


METHODS
TIM-3 and PD-1 expression by peripheral and decidual immune cells from pregnant BALB-c mice in 2 weeks of gestational age were measures by flow cytometry. Placental galectin-9 expression was determined by immunohistochemically and RT-PCR.


RESULTS
Gal-9 was found to be present in the spongiotrophoblast layer of the haemochorial placenta. Decidual NK, NKT and γ/δ T cells showed increased PD-1 expression and reduced cytotoxic potential when compared to the periphery. TIM-3 expression by NK cells and γ/δ T cells is similar both in the periphery and in the decidua, notably, their relative TIM-3 expression is increased locally which is associated with reduced lytic activity. Decidual NKT cells exhibit a reduced TIM-3 expression with increased relative receptor expression and a slightly increased cytotoxicity when compared to the periphery.


CONCLUSIONS
Our data reveals a particularly complex, tissue and cell type specific immunoregulatory mechanism by the investigated co-inhibitory receptors at the fetomaternal interface.
University of Pecs, Clinical Centre, Department of Medical Microbiology and Immunology, Pecs, Hungary; Janos Szentagothai Research Centre, Pecs, Hungary.
Matyas
M
Meggyes
University of Pecs, Clinical Centre, Department of Medical Microbiology and Immunology, Pecs, Hungary.
Adrienn
A
Lajko
University of Pecs, Clinical Centre, Department of Medical Microbiology and Immunology, Pecs, Hungary; Janos Szentagothai Research Centre, Pecs, Hungary.
Tamas
T
Palkovics
University of Pecs, Clinical Centre, Department of Medical Microbiology and Immunology, Pecs, Hungary.
Anett
A
Totsimon
Department of Neurology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Zsolt
Z
Illes
University of Pecs, Clinical Centre, Department of Medical Microbiology and Immunology, Pecs, Hungary; Janos Szentagothai Research Centre, Pecs, Hungary. Electronic address: szereday.laszlo@pte.hu.
Laszlo
L
Szereday
University of Pecs, Clinical Centre, Department of Medical Microbiology and Immunology, Pecs, Hungary; Janos Szentagothai Research Centre, Pecs, Hungary.
Eva
E
Miko
D000818:Animals; D005260:Female; D037161:Galectins / Q000378:metabolism*; D000072597:Hepatitis A Virus Cellular Receptor 2; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*
D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011991:Receptors, Virus; C508186:galectin 9, mouse
Feto-maternal interface; Gal-9; Immunity; PD-1; Pregnancy; TIM-3