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 numerous germline-encoded pattern recognition receptors (PRR). These receptors include Toll-like receptors (TLR), NOD-like receptors (NLR), RIG-I-like RNA helicases and C-type lectin receptors.
TLRs have been extensively studied in this innate-adaptive interface, however a new class of PRRs, the NOD-like receptors, has recently been found to also regulate adaptive immune responses. However, for a majority of the 22 known NLR human family members, their triggers and physiologic function remain unknown.
Our lab focuses specifically on the role of NLRs in shaping adaptive immunity. We discovered that the NLR Nlrp3, which forms an inflammasome with caspase-1 and ASC, is critical in the adjuvant function of aluminum hydroxide and nanoparticles during vaccination. Yet how inflammasome activation regulates adaptive immunity is still a mystery. Further, we have found that a number of novel NLR family members are also critical in the initiation of T and B cells responses. We are actively working on answering these questions in the context of animal autoimmunity and vaccine models as well as in human studies.
- Identifying the triggers and physiological function of novel NLR family members
- How Nlrp3 regulates immunity following vaccination with alum adjuvants and nanoparticles
- Regulation of the autoimmune disease, multiple sclerosis, by caspase-1 in mice and humans
- Characterizing the molecular pathways critical in regulating NLR activation and effector function
- Identifying innate immune receptors critical to red blood cell alloimmunization