Vascular injury derived apoptotic exosome-like vesicles trigger autoimmunity

Area of Science:

• Immunology
• Autoimmunity
• Cell Biology

Background:

• Classical immune theory posits healthy systems avoid self-reactive lymphocytes, yet autoreactivity exists in B cells.
• Autoreactive B cells are believed to depend on self-ligands for selection and survival.

Purpose of the Study:

• To investigate the immune-stimulating functions of exosome-like structures from apoptotic endothelial cells (ApoExos).
• To identify mechanisms driving autoantibody production in healthy individuals.

Main Methods:

• Stimulation of self-reactive B cells in vitro with toll-like receptor (TLR) agonists.
• Injection of ApoExos into healthy mice to assess immune responses.
• Analysis of autoantibody production and T cell involvement.

Main Results:

• Healthy mice exhibit self-reactive B cells secreting anti-LG3/perlecan upon TLR stimulation.
• ApoExos injection activates the IL-23/IL-17 axis and induces autoantibodies, including anti-LG3 and lupus-associated autoantibodies.
• γδT cells mediate the maturation of ApoExos-induced autoantibodies.

Conclusions:

• Apoptotic endothelial cell-derived exosomes (ApoExos) possess immune-mediating functions, stimulating normal B cells to produce autoantibodies.
• Toll-like receptor (TLR) activation and γδT cells are critical modulators of ApoExos-induced humoral autoimmune responses.