A new research has revealed that a human peptide called LL37, when coupled with body's own DNA, works as a natural antibiotic against invading microbes.
The research team, led by scientists at The University of Texas M. D. Anderson Cancer Center, reported their finding in an early online publication of Nature.
Advertisement"This combination of the peptide and self-DNA activates the same immune response pathway as a virus does," Nature quoted senior author Michel Gilliet, M.D., assistant professor in M. D. Anderson's Departments of Immunology and Melanoma Medical Oncology, as saying.
According to the researchers, this immune response is both a likely key driver of autoimmune disease and an early warning system that flags tissue damage to launch a protective inflammatory response to injury. "We show that this pathway may drive autoimmunity in psoriasis, a chronic inflammatory skin disease," Gilliet said.
The key peptide is also heavily expressed in other autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. The key peptide, called LL37 not only provides a new potential target to block in the treatment of constant inflammatory diseases but also acts as a possible component for vaccines against infectious diseases and cancers.
The research team found the new pathway by studying the activation of important immune defense cells in psoriasis. Plasmacytoid dendritic cells (pDCs) are highly specialized to recognize viral and other microbial infections. They engulf a virus and set off an immune system cascade to fight the infection by producing interferons.
The researchers previously showed that pDC activation in psoriatic skin drives the development of human psoriasis. "These dendritic cells normally do not respond to self-DNA," Gilliet explained. Dendritic cells' insensitivity prevents the cells from launching an attack on the body's own tissue.
However, researchers had accumulated evidence of a link between skin damage with release of self-DNA and pDC activation in psoriatic skin leading to disease formation. They lacked a molecular mechanism connecting these factors.
Research involved a series of lab experiments and identified that LL37 as the key ingredient in psoriatic tissue that activates the dendritic cells. The peptide is a member of a family of antimicrobial peptides long known to defend against infection through their ability to directly destroy bacteria and viruses.
The research concluded that LL37 activates the dendritic cells by binding to the self-DNA to form a structure that allows it into the dendritic cells, as if it were an invading microbe.
"We think LL37's normal job is to alert the immune system to tissue damage and stimulate a temporary inflammatory response that enhances resistance to infection and initiates wound healing. When tissue is injured, cells are destroyed and they spill DNA into the areas surrounding the cells. LL37, released by epithelial cells, binds this extracellular DNA, which is then taken up by the pDCs to launch the protective inflammatory immune response," Gilliet said.