The role of integrins and TGF-beta in regulating immune responses
The immune system has evolved to protect the body from harmful pathogens. To function properly, the immune system must be tightly regulated so that it is switched on/off only at appropriate times and in appropriate locations in the body. When this regulation is compromised, disease situations can arise- for example, overwhelming infection if the immune system is not activated appropriately in response to pathogens, or autoimmune disease (e.g. inflammatory bowel disease, diabetes, arthritis) if the immune system is not prevented from attacking self-tissues. Therefore, understanding the factors and pathways that are important in regulation of the immune system will be important in understanding pathologies caused by abberant immune responses.
Our work focuses on a key molecule involved in regulating the immune system: the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta). TGF-beta is secreted from cells in an inactive form that needs to be activated to exert effects on TGF-beta receptor-expressing cells. We have recently identified the integrin receptor, alphavbeta8, as an important activator of TGF-beta in the immune system. Disruption of this pathway results in a loss of immune homeostasis, resulting in self-harmful immune responses.
Our current research focuses on understanding the mechanisms and important biological outcomes of integrin-mediated TGF-beta activation in the immune system. Specifically, how is integrin-mediated TGF-beta activation controlled? How does this process affect other immune cell types in order to mediate its function? What other biological outcomes are controlled by integrin-mediated TGF-beta activation? Answering these questions will provide important insights into how TGF-beta functions, and the pathways by which TGF-beta tightly regulates immune responses.