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

Area of Science:

• Immunology
• Reproductive Biology
• Cell Biology

Background:

• Heat shock proteins (HSP70), including constitutive Hsc70 and inducible Hsp70, play roles in cellular stress responses.
• Decidual immune cells, particularly dendritic cells (DCs), are crucial for maintaining immune tolerance during pregnancy.
• Toll-like receptor 4 (TLR4) and CD91 are cell surface receptors involved in immune cell activation and recognition.

Purpose of the Study:

• To investigate the binding of HSP70 to TLR4 and CD91 receptors on decidual CD1a(+) DCs.
• To determine the effect of HSP70 binding on the maturation status of decidual DCs.
• To analyze the influence of HSP70 on cytokine and chemokine profiles in the decidual microenvironment.

Main Methods:

• Immunohistology and immunofluorescence were used to examine decidual tissue from early and term pregnancy.
• Flow cytometry was employed to detect DC antigens and assess changes after stimulation with HSP70.
• Decidual mononuclear cells were stimulated with HSP70 to evaluate its effects on DC maturation markers and cytokine production.

Main Results:

• HSP70 was detected intracellularly and in the nucleus of trophoblast cells, with higher levels in early pregnancy decidua.
• HSP70 demonstrated binding to CD91 and TLR4 receptors on decidual CD1a(+) DCs.
• HSP70 stimulation led to increased expression of maturation markers (CD83, HLA-DR, CD80, CD86) and altered chemokine receptor (CCR5) and ligand (CCL3, CCL22) profiles.
• HSP70 significantly increased the production of interferon-gamma and interleukin-15, favoring a Th1 immune response.

Conclusions:

• HSP70 binds to CD91 and TLR4 on decidual DCs, inducing their maturation.
• HSP70 promotes a Th1-biased cytokine and chemokine environment.
• This immune modulation by HSP70 may potentially contribute to adverse immune responses during pregnancy.