Involvement of Galectin-9/TIM-3 pathway in the systemic inflammatory response in early-onset preeclampsia.
BACKGROUND
Preeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction.


METHODS
The aim of our study was to investigate the expression and function of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells and the possible role of Galectin-9/TIM-3 pathway in the immunoregulation of healthy pregnancy and early-onset preeclampsia. We determined TIM-3 and Gal-9 expression and cytotoxicicty of peripheral lymphocytes of early-onset preeclamptic women and healthy pregnant woman using flow cytometry.


RESULTS
Investigating peripheral lymphocytes of women with early-onset preeclampsia, our results showed a decreased TIM-3 expression by T cells, cytotoxic T cells, NK cells and CD56(dim) NK cells compared to healthy pregnant women. Interestingly, we found a notably increased frequency of Galectin-9 positive cells in each investigated lymphocyte population in the case of early-onset preeclamptic patients. We further demonstrated increased cytotoxic activity by cytotoxic T and CD56(dim) NK cells in women with early-onset preeclampsia. Our findings showed that the strongest cellular cytotoxic response of lymphocytes occurred in the TIM-3 positive subpopulations of different lymphocytes subsets in early-onset preeclampsia.


CONCLUSIONS
These data suggest that Gal-9/TIM-3 pathway could play an important role in the immune regulation during pregnancy and the altered Galectin-9 and TIM-3 expression could result an enhanced systemic inflammatory response including the activation of Th1 lymphocytes in preeclampsia.
Department of Medical Microbiology and Immunology, Clinical Centre, University of Pecs, Pecs, Hungary.
Eva
E
Miko
Matyas
M
Meggyes
Barbara
B
Bogar
Nora
N
Schmitz
Aliz
A
Barakonyi
Akos
A
Varnagy
Balint
B
Farkas
Peter
P
Tamas
Jozsef
J
Bodis
Julia
J
Szekeres-Bartho
Zsolt
Z
Illes
Laszlo
L
Szereday
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D037161:Galectins / Q000378:metabolism*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007249:Inflammation; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D010641:Phenotype; D011225:Pre-Eclampsia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins