Investigators from Osaka University have isolated a neurological protein involved in the activation of immune cells that typically protect against inflammatory disorders. This discovery is crucial because it can lead to the development of new treatments for inflammatory diseases.
The immune cells known as macrophages are categorized as M1 or M2 inflammatory macrophages. The M1 cells participate in the inflammatory response that destroys invading organisms, while M2 cells hold anti-inflammatory properties that are believed to protect against inflammatory diseases.
The investigators were aware that before these macrophages carried out their intended roles, they must first be activated and transformed into either the M1 or the M2 subtype. However, the mechanisms behind macrophage subtype commitment are not fully understood.
The current study, as reported in Nature Immunology, has isolated a protein that drives macrophages to differentiate into the M2 type, which protects against inflammatory conditions. The M1 and M2 macrophage populations hold differing energy needs, so the macrophages must be able to sense and respond to nutrients in their surroundings as part of the activation process. The research team investigated a cell signaling pathway that forces macrophages to form the M2 subtype, this signaling pathway is known as mTOR.
Investigators utilized used a chemical inhibitor that stops the activity of the mTOR protein using and enables them to observe how other proteins in the pathway were affected.
Surprisingly, the study led to the identification of a protein by the name of Sema6D, known for its role in neuronal guidance during nervous system development. So, when M2 macrophages were genetically engineered, they did not contain Sema6D.
Without Sema6D protein, the macrophages are unable to undergo transformation into the M2 cell population. Once M2 differentiation can be inhibited, investigators realized how this might affect the protective role of these cells in inflammatory conditions.
Lead researcher Atsushi Kumanogoh believes the research findings conclude that Sema6D inactivation prevents M2 differentiation, which causes the body to be more susceptible to inflammatory conditions.
"We’re hopeful that this discovery offers new leads in the drug discovery process for these diseases,” notes Kumanogoh.
Source: Alpha Galileo
