Researchers have found a method to control irregular immune responses and treat autoimmune diseases. Chemical optogenetic modulation, i.e. light-controlled chemical enzymes, can effectively control and suppress chronic inflammatory problems.
Inflammation is a complex physiological response of the immune system that serves as the first line of defense against pathogens. The human immune system consists of different specialized immune cells that orchestrate our bodies’ immune responses. These immune cells control and regulate inflammation through pro-and anti- inflammatory signals. Macrophages are one such type of immune cells that initiate an immune response. In some cases, deregulation of immune responses can lead to an imbalance in these signals, leading to chronic inflammation and other inflammatory disorders.
It is an established fact that histone deacetylases (HDAC), a type of enzymes, influence the behavior of macrophages. The inhibition of these naturally-occurring HDACs can reduce the pro-inflammatory signals released by macrophages and hence control inflammation. Although HDAC inhibitors have been used clinically and pre-clinically for treatment of neurodegenerative diseases and cancer, they can cause toxic side effects in the body. A research study published in the Royal Society of Chemistry describes a method to modulate the inflammatory signals using HDAC inhibitors administered using UV irradiation. Here, they describe a unique method to deliver HDAC inhibitors only to localized tissue.
Chemical optogenetics is a way of using light and small molecule probes to study and manipulate biological processes. In this study, researchers used a photo-controlled (light-controlled) chemical strategy to deliver HDAC inhibitors to affected tissue. Here, the inhibitors are released in the vicinity of the target cells and thus highly reduce the possibility of side effects. The inhibitors bind with HDACs within macrophages and decrease inflammation in the area.
A cell-permeable HDAC inhibitor, Suberoylanilide hydroxamic acid (SAHA), is released in the tissue with spatiotemporal control. In order to control its release, it is bound to a photo-removable protecting group 6-nitroveratryl (NV). This group is released from its bond with SAHA when irradiated with a UV light irradiation, allowing the inhibitor SAHA to carry out its role. The release of SAHA yielded in macrophage modulation, reducing inflammation in the local area without toxic side effects.
The results indicate an effective control and modulation of inflammation is possible using UV radiation and chemical enzymes. This is especially useful in the treatment of autoimmune diseases and cancer. The precise control achieved using this methodology ensures that no immunosuppression occurs in the body other than the target areas. Selective delivery of inhibitors can have anti-inflammatory effects on various immune cell types and result in a desirable physiological outcome.
Written By: Ahuja Galagali, Biomedical Engineer