Reducing ADAM12 protein can limit activation of overly active immune cells in MS
INFLAMMATORY DISEASE In a new study, researchers from the Issazadeh-Navikas group, BRIC, show that the protein ADAM12 plays an essential role in the function of immune cells and that reducing the protein can limit the activation of overly active immune cells in inflammatory diseases, such as MS. The results have just been published in Cellular & Molecular Immunology by Nature Publishing.
ADAM12 essential for the function of immune cells
Immune-mediated inflammatory diseases are caused by dysregulation of the immune response, where immune cells become hyperactive and cause inflammation - thereby damaging the brain instead of protecting it. One type of immune cell in particular - known as Th1 - has proven to play an important role in inflammatory diseases.
In their new study, the researchers from BRIC examined the function of a certain molecule, called ADAM12, in Th1 cells. The ADAM12 protein is known to be involved in regulating many cell functions, such as differentiation, cell growth and cell interaction.
When the researchers examined the function of ADAM12 in T cells in disease models, they discovered that ADAM12 is also essential for the function of Th1 cells.
By genetically reducing ADAM12, the researchers were able to limit the activation of Th1 cells, potentially regulating inflammatory disease:
“Through this study, it has for the first time been discovered that genetic loss of ADAM12 alleviates the activation of a type of T cell, called Th1. ADAM12 can be actively involved in the outcome of tissue-specific inflammatory processes, such as neuroinflammation in a model of MS and skin inflammation in a model of dermatitis”, says Yawei Liu, Associate Professor in the Issazadeh-Navikas group.
ADAM12 molecule (Adopted figure from Biochim Biophys Acta.2013 Oct; 1830(10): 4445-4456)
Potential future target for inflammatory diseases
The Issazadeh-Navikas group is now attempting to better understand the function of ADAM12 and its target cells for the regulation of tissue inflammation. In the future, this knowledge can prove useful in relation to inflammatory diseases in general.
“T cell function regulates many diseases, and therefore, this study broadens our knowledge of inflammation and disease progression, encouraging research in this area to meet the increased interests and needs of society. Additionally, ADAM12 could serve as a new target for diseases that are caused by Th1 cells and the activation of Th1-mediated anti-tumor therapy”, says Liu.
Figure legend ADAM12 a specific Th1 cell costimulatory molecule important for induction of tissue inflammation
Cell-surface transmembrane ADAM12 acts as a specific costimulatory molecule on a subset of T cells. Under the conditions that T cells lack ADAM12 signaling, this results in defective Th1 cell generation and poor tissue inflammation.
Read the full paper in Cellular & Molecular Immunology by Nature Publishing.