The enemy within: endogenous retroelements and autoimmune disease.

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Autoimmune diseases are often caused by the innate immune system's inappropriate detection of self nucleic acids.
• Endogenous retroelements, which are integrated into the host genome, can produce nucleic acids that trigger immune responses.

Purpose of the Study:

• To identify unexpected sources of endogenous immunostimulatory nucleic acids.
• To explore the implications of retroelement cDNA detection by the innate immune system on immune responses to infectious retroviruses like HIV.
• To propose an evolutionary tradeoff influencing the DNA-activated antiviral response.

Main Methods:

• Review of existing literature on innate immunity, nucleic acid sensing, and retroelement biology.
• Analysis of the evolutionary pressures shaping antiviral responses.
• Discussion of potential therapeutic strategies targeting the intersection of retroelement biology and innate immunity.

Main Results:

• Reverse-transcribed cDNA from endogenous retroelements represents an unexpected source of immunostimulatory nucleic acids.
• The innate immune system's sensing and clearance of retroelement cDNA are critical for understanding responses to infectious retroviruses (e.g., HIV).
• An evolutionary tradeoff exists where a strong antiviral response to infectious retroviruses may lead to inappropriate detection of endogenous retroelements.

Conclusions:

• The detection of endogenous retroelement cDNA by the innate immune system has significant implications for autoimmune diseases.
• Evolutionary selection for robust antiviral immunity may predispose individuals to autoimmunity via endogenous retroelement recognition.
• Understanding this interplay can inform novel therapeutic approaches for autoimmune conditions.