Heat-Shock Proteins 70 Induce Pro-Inflammatory Maturation Program in Decidual CD1a(+) Dendritic Cells

Am J Reprod Immunol. 2015 Jul;74(1):38-53. doi: 10.1111/aji.12374. Epub 2015 Mar 4.

Abstract

Problem: 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.

Method of study: 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.

Conclusion: 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.

Keywords: Antigen-presenting cells; HSP70; chemokine; cytokine; interleukin-15; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD1 / immunology
  • B7-1 Antigen / biosynthesis
  • B7-2 Antigen / biosynthesis
  • CD83 Antigen
  • Chemokine CCL22 / metabolism
  • Chemokine CCL3 / metabolism
  • Decidua / cytology
  • Decidua / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • HLA-DR Antigens / biosynthesis
  • HSC70 Heat-Shock Proteins / immunology
  • HSC70 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunoglobulins / biosynthesis
  • Inflammation
  • Interferon-gamma / immunology
  • Interleukin-15 / immunology
  • Low Density Lipoprotein Receptor-Related Protein-1 / immunology
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Membrane Glycoproteins / biosynthesis
  • Pregnancy
  • Protein Binding
  • Th1 Cells / immunology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism*
  • Trophoblasts / cytology

Substances

  • Antigens, CD
  • Antigens, CD1
  • B7-1 Antigen
  • B7-2 Antigen
  • CCL22 protein, human
  • CCL3 protein, human
  • CD1a antigen
  • CD86 protein, human
  • Chemokine CCL22
  • Chemokine CCL3
  • HLA-DR Antigens
  • HSC70 Heat-Shock Proteins
  • IL15 protein, human
  • Immunoglobulins
  • Interleukin-15
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Glycoproteins
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Interferon-gamma