Grant: Team Grant: P/T Inflammation for Chronic Conditions-HIV/AIDS Research Initiative

Excessive inflammation can cause tissue damage and disease, yet at mucosal surfaces some amount of inflammation is necessary and/or inevitable due to ongoing antigenic exposure, which includes possible pathogens and "friendly" bacteria. The difficulty in treating diseases with an underlying inflammatory aspect is specifically targeting the "bad" aspects of inflammation while retaining what is required for normal function of the tissue. CD4+ T cells are a type of white blood cell that are often at the centre of determining what type of immune responses will develop, and also play important regulatory functions in maintaining a normal state of "homeostasis". A certain type of CD4+ T cell called a "Th17" cell has been implicated in various inflammatory diseases including autoimmunity, inflammatory bowel disease, and HIV infection. These cells respond to a wide variety of "antigens" (proteins seen as foreign to the immune system), secreting a variety of cytokines. Th17 cells come in different varieties, including those that are more inflammatory and those that maintain mucosal integrity. These different subsets can be defined by their cytokine profiles and which other molecules they express on the surface and within the cell. Both are often present, in varying ratios, and this ratio might be important for deciding whether the balance tips in favour of inflammation or not. Here we hypothesize that approaches targeting and reducing the inflammatory th17 subset more specifically will be safer and better able to prevent immunopathology. In this grant we will explore and define these alternate Th17 pathways in more detail, in different clinically relevant contexts, to better understand how this immune subset can be targeted with more precision in the clinic to improve mucosal health.