Infection, autoimmunity and autoimmune disease

Area of Science:

• Immunology
• Autoimmunity
• Molecular Biology

Background:

• Heat shock proteins (HSPs), specifically hsp60 and hsp70, are highly conserved and immunodominant in mammalian immune responses to infections.
• Their high conservation raises concerns about potential autoimmunity and autoimmune disease development during infection defense.
• Previous understanding suggested autoimmunity inevitably leads to disease, but research on HSP immune responses challenges this view.

Purpose of the Study:

• To investigate the role of immune responses to heat shock proteins (HSPs) in the context of autoimmune diseases.
• To explore whether modulating autoimmunity to HSPs can prevent or treat autoimmune conditions.
• To assess the feasibility of using HSPs as a therapeutic strategy for autoimmune diseases.

Main Methods:

• Studied immune responses to HSPs in animal models of autoimmune diseases, including adjuvant arthritis in Lewis rats and insulin-dependent diabetes in NOD mice.
• Examined the effects of modulating autoimmunity to HSPs on disease development and progression.
• Investigated the potential of immunization with HSPs as a treatment modality.

Main Results:

• Demonstrated that modulation of autoimmunity to HSPs can prevent autoimmune disease development in animal models.
• Showed that immunization with HSPs can be a feasible treatment for existing autoimmune diseases, as evidenced in adjuvant arthritis and diabetes models.
• Identified HSP60 and HSP70 as ubiquitous proteins involved in regulatory loops of autoimmunity.

Conclusions:

• Immune responses to highly conserved heat shock proteins (HSPs) can be modulated to prevent and treat autoimmune diseases.
• HSP-based strategies offer a promising therapeutic avenue for autoimmune conditions, even when the specific autoantigen is unknown.
• This research redefines the relationship between autoimmunity and autoimmune disease, highlighting a potential for immune tolerance induction via HSPs.