Heat-Shock Proteins 70 Induce Pro-Inflammatory Maturation Program in Decidual CD1a(+) Dendritic Cells.
OBJECTIVE
The aim of the study was to assess possible binding of a mixture of constitutive Hsc70 and inducible Hsp70 forms (HSP70) to Toll-like receptor (TLR) 4 and CD91 receptors on decidual CD1a(+) dendritic cells (DCs) and their influence on DCs maturation status.


METHODS
Immunohistology and immunofluorescence of paraffin-embedded first trimetester and term pregnancy decidua were performed together with flow cytometry detection of antigens in DCs after stimulation of decidual mononuclear cells with HSP70.


RESULTS
Hsc70 and Hsp70 labeling revealed intracellular and nuclear staining in trophoblast cells. The numbers of Hsc70(+) and Hsp70(+) cells of decidual tissue were higher in early pregnancy decidua than in decidua at term. HSP70 binds CD91 and TLR4 receptors on CD1a(+) DCs and increased the expression of CD83, HLA-DR, CD80, and CD86, but decreased CC receptor (CCR) 5. HSP70 increased CC ligand (CCL) 3 and CCL22. HSP70 in the concentration of 1 μg/mL increased the percentage of interferon-γ and interleukin (IL)-15-expressing cells over the cells expressing IL-4.


CONCLUSIONS
HSP70 binds CD91 and TLR4 on decidual CD1a(+) DCs, causes their maturation, and increases IL-15 in the context of Th1 cytokine/chemokine domination, which could support immune response harmful for ongoing pregnancy.
Department of Radiotherapy and Oncology, Clinical Hospital Centre Rijeka, Rijeka, Croatia.
Arnela
A
Redzovic
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Tamara
T
Gulic
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Gordana
G
Laskarin
Department of Pathology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Senija
S
Eminovic
Department of Obstetrics and Gynecology, Clinical Hospital, University of Rijeka, Rijeka, Croatia.
Herman
H
Haller
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.|Department of Clinical and Transplantation Immunology and Molecular Medicine in Rijeka, Croatian Academy of Sciences and Arts, Rijeka, Croatia.
Daniel
D
Rukavina
D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D054422:Chemokine CCL22 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D050883:HSC70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D011247:Pregnancy; D011485:Protein Binding; D018417:Th1 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology; D000097802:CD83 Antigen
D015703:Antigens, CD; D018949:Antigens, CD1; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D054422:Chemokine CCL22; D054405:Chemokine CCL3; D006684:HLA-DR Antigens; D050883:HSC70 Heat-Shock Proteins; D007136:Immunoglobulins; D007371:Interferon-gamma; D019409:Interleukin-15; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D051197:Toll-Like Receptor 4; D000097802:CD83 Antigen; C515482:CCL22 protein, human; C515429:CCL3 protein, human; C419393:CD1a antigen; C497964:CD86 protein, human; C569274:IL15 protein, human; C475476:LRP1 protein, human; C495345:TLR4 protein, human
Antigen-presenting cells; HSP70; chemokine; cytokine; interleukin-15; pregnancy