Fight Aging!

The inflammatory cytokine TNF is the target of many efforts to find ways to reduce inflammation in conditions characterized by excessive inflammatory activity of the immune system, such as autoimmune diseases. It is a blunt approach, as it reduces not only inappropriate activity, but also the needed activity of the immune system, such as defense against pathogens and destruction of potentially cancerous and senescent cells. The methods of targeting TNF are becoming ever more sophisticated, as this example demonstrates. It is nonetheless the case that better and different classes of treatment will be needed in order to avoid the issue of reducing the capacity of the immune system to carry out necessary tasks.

Researchers describe how novel nanomaterials could assemble into long nanofibers that include a specialized protein, called C3dg. These fibers then were able to activate immune system B-cells to generate antibodies. Due to the protein's ability to interface between different cells in the immune system and activate the creation of antibodies without causing inflammation, researchers have been exploring how C3dg could be used as a vaccine adjuvant, which is a protein that can help boost the immune response to a desired target or pathogen.

In their new nanomaterial, researchers were able put this idea to the test by weaving key fragments of the C3dg protein with epitopes of TNF into nanofibers. The C3dg protein would trigger the B-cells to create antibodies, while the TNF epitopes would provide a blueprint of what the antibodies need to seek out and destroy. "We saw that there was a strong B-cell response, which means there was an increased production of antibodies that targeted TNF. When we delivered the C3dg nanofibers into mice, it was highly protective, and the mice didn't experience an inflammatory response."

When the team tested their nanomaterial in a psoriasis mouse model, they found that the nanofibers carrying C3dg were as effective as a monoclonal antibody therapy targeting TNF. And because C3dg is normally found in the body, it wasn't flushed out of the system by anti-drug antibodies. After examining the psoriasis model, the team made a surprising discovery - C3dg wasn't just stimulating antibody production in the B-cells, it was also influencing the response of T-cells. For their next steps, the team hopes to further explore the mechanisms behind this beneficial T-cell activation. They'll also pursue additional experiments to explore the response to similar nanomaterials in rheumatoid arthritis models.

Link: https://pratt.duke.edu/about/news/self-assembling-nanofibers-prevent-damage-inflammation