Led by researchers from Mount Sinai's Icahn School of Medicine, a team of scientists discovered a key protein that can tap into the immune system to significantly boost healing.
Published in the journal Cell Reports, the study involves proteinases, focusing on matrix metalloproteinases (MMPs) in particular that target the non-cell structural framework within tissues. Researchers found that aside from targeting the extracellular matrix, a specific type of MMPs known as MMP-2 has the ability to control the immune system, shifting certain sets of cells to facilitate immune response and speed up healing. However, MMP-2 in action also has the potential to worsen inflammations in the body.
With this discovery, pharmaceutical companies can leverage these actions by MMP-2 to create drugs that can promote wound healing or prevent inflammatory cues that will spur autoimmune diseases and encourage tumor growth.
"Our results show that MMP-2 uses a multitude of mechanisms to modulate the immune system. These data provides context to how this mechanism happens and could lead to novel treatments," explained Nina Bhardwaj, M.D., Ph.D., immunotherapy director at the Mount Sinai Tisch Cancer Center and lead investigator for the study.
The study is based on the premise that when dendritic cells are exposed to MMP-2s, a protein known as OX40L is made. When OX40L is expressed, the process sends out other signals, one of which stimulates the creation of immune system cells TH2. While effective in healing wounds, TH2 sometimes triggers the release of antibodies that makes the body attack its own cells, encouraging inflammation that aggravates conditions like lupus and rheumatoid arthritis. Additionally, the cytokines that TH2 produces efficiently fights parasitic infections but unfortunately fuels autoimmune diseases in large amounts.
Bhardwaj adds that MMP-2-mediated signals either via mimics or direct injections could stimulate wound healing but proposed functions will need further research using disease-specific models. If new MMP-2 functions are discovered, it could lead to the discovery as well of new inflammatory response reagents.
This study received support from the National Institutes of Health, the American Cancer Society, the Bill and Melinda Gates Foundation, the Melanoma Research Alliance, the Alliance for Lupus Research, the Ludwig Institute for Cancer and the Cancer Research Institute. Researchers from the Institut National de la Sante et de la Recherhe Medicale, Emory University, New York University, Stanford University, and Rockefeller University also contributed.
Co-authors include: Sergio Trombetta, Francine Jotereau, Bali Pulendran, Rajesh Ravindran, Yichun Fu, Yvonne Saenger, Ngozi Monu, Navpreet Tung, Miriam Merad, Juliana Idoyaga, Anne Gallois and Emmanuelle Godefroy.