Research Interests:The main interest of our lab is on how cytokine expression and function is regulation during infection and inflammatory responses in human immune system cells. In particular our projects are focused on examining the roles played by the IL-12 family of cytokines in immune responses.
1) The IL-12 family of cytokines in HIV Immunopathogenesis:
Human immunodeficiency virus (HIV) infection results in Acquired Immunodeficiency Syndrome (AIDS) and is affecting the population worldwide. HIV and AIDS result in the progressive loss of the patients' immune system function and ability to clear and recover from not only the HIV infection, but other opportunistic infectious diseases. The virus uses a variety of mechanisms to escape the host immune system, including deregulation of cytokine production. The focus of our research is on how HIV can disable cytokine production and function.
HIV infection of CD4+ T cells and monocytic cells results in the loss of general and HIV-specific immunity. Deregulation of cytokines, such as IL-12, by the virus may play a role in the pathogenesis of AIDS. Research in our lab focuses on defining how HIV infection modulates the IL-12 family of cytokines in primary monocytic cells and in monocyte-derived macrophages and dendritic cells. This family of cytokines is comprised of three heterodimeric cytokines: IL-12, IL-23, and IL-27, all of which play a role in T cell development and in the regulation of inflammatory responses. How HIV affects the function of these cytokines is not clear at present; however, recent work from our lab has demonstrated that HIV infection can impact IL-27 serum expression levels. We are currently investigating further into this aspect of HIV infection and how the functions of IL-27 are impacted by HIV infection.
2) The IL-12 family of cytokines in inflammation:
Inflammation is one of the defence systems set up by our body that helps us combat microbial infections. There are different cells in the human immune system that are responsible for directing the immune system's response. Of these cells, monocytes/macrophages orchestrate innate inflammatory responses directed by cytokines released to the cell microenvironment. We have demonstrated that a key immunoregulatory cytokine, IL-27, secreted in response to microbial infection/TLR triggering, activates monocytic cells to secrete proinflammatory cytokines. IL-27 functions to link the innate and adaptive immune response achieved by its ability to initiate proinflammatory cytokine expression by monocytes/macrophages and by its ability to regulate T helper cell differentiation. If inflammation is not regulated properly, this may prevent the immune system from defending against infections and may even lead to the development of autoimmune diseases. Our lab focuses on how the IL-12 family of cytokines, in particular IL-27, serves to regulate inflammatory responses.