Inflammation is a vital physiological process in infection and tissue repair after injury, but uncontrolled, chronic inflammation occurs in many diseases, including cancer, colitis and autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and Type 1 diabetes. Current antiinflammatory drugs are delivered systemically and cause of ftarget effects in otherwise healthy tissues, and thus, there is a great demand for next generation technologies to locally inhibit activation of the immune system, whose cells are the major source of inflammation in vivo, to limit these side effects. In this proposal, we aim to develop precision chemical tools to inhibit local inflammation by modulating the functions of select target populations of immune cells and apply these tools to both study fundamental biological mechanisms of inflammatory pathways and control the immune response in therapeutic settings.