The mammalian immune system can be divided into two arms that act together to provide both immediate and long-term immunity to pathogens, the innate and adaptive immune branches, respectively. The more primitive innate branch of the immune system provides critical regulation of adaptive immunity, in part through activity of numerous pattern recognition receptors (PRRs). These receptors include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like RNA helicases (RLRs) and C-type lectin receptors (CLRs). Triggering of such receptors is a key pathway by which dendritic cell (DC) activation is achieved. DCs survey tissue for infection/damage and translate this information into signals that regulate the activation of T cells to drive inflammation. In a process that is poorly understood, the emigration of activated DCs from an inflamed tissue is a crucial checkpoint in the generation of a productive T cell-driven adaptive immune response.
Our lab focuses specifically on the role of DCs in shaping adaptive immunity and the stimuli that guide their activation. We recently identified an unexpected role for a molecule that regulates the actin cytoskeleton, Dock8, in dictating whether certain types of DCs can migrate to lymph nodes or within the spleen. By disturbing the movement of certain DCs during the course of an immune response we can block adaptive immunity to a given insult. Beyond DC migration from a tissue, we have further found that the spatial organization of different types of DCs after immunization specifies the type of T cell activated and the particular effector response induced. The lab is currently working on understanding the signals that dictate this unique cellular organization and how that informs T cell fate. Our ultimate goal is to modulate DC movement in order to promote wanted immune responses and conversely block those that are deleterious.
· Identifying which DCs can induce a productive Tfh-driven antibody response and how
· How is induction of IgE to aeroallergens regulated
· How is the immune response to food antigens induced
· Characterizing the molecular pathways that regulate DC migration
· Identifying innate immune receptors that trigger red blood cell alloimmunization