Research Lab of Jonathan Boyson, Ph.D.
Areas of interest: Molecular Determinants of iNKT cell Activation by CD1d and its Ligands.
Dr. Boyson is interested in examining the function of iNKT cells which comprise an unusual lymphocyte subset with regulatory properties. iNKT cells have been demonstrated to play critical roles in tumor immunology, autoimmunity, tolerance induction, and infectious disease. Unlike most T cells which recognize peptides bound by class I MHC molecules, iNKT cells recognize glycosphingolipids presented by the monomorphic class I MHC-like molecule CD1d. One major focus, therefore, is to elucidate the mechanisms through which glycosphingolipids interact with the iNKT T cell receptor and to understand the mechanisms controlling glycosphingolipid biosynthesis. His group is also interested in developing an animal model in which to study iNKT cell function. Currently, we are examining possible roles of iNKT cells at the maternal-fetal interface. iNKT cell activation leads to rapid pregnancy in mice. By elucidating the mechanisms through which this occurs, we hope to understand whether these cells play a role in regulating the maternal response to the semi-allogeneic fetus. Dr. Boyson’s group has recently identified a congenic interval, the SLAM locus, which controls strain-dependent differences in NKT cell number and function. His group is pursuing the identification of the gene(s) in collaboration with Dr. Teuscher. In addition, he is also collaborating with Dr. Budd on a project investigating the effect of this congenic interval on NKT cell homeostasis, and with Dr. Wargo on a project investigating the function of CD1d on lung epithelial cells.
Programs & Projects
Semi-invariant NKT cells comprise an unusual, highly conserved, lymphocyte subset that has been implicated in tolerance induction, tumor immunology, autoimmunity, and infectious disease. Unlike most T cells which recognize peptide bound by class I MHC molecules, iNKT cells bind glycolipids bound by the class I MHC-like molecule CD1d. Upon activation, NKT cells produce both Th1 (e.g., IFN-gamma and TNF-alpha) as well as Th2 (e.g., IL-4, IL-10, and IL-13) cytokines. Accordingly, they have been observed to play roles in both pro-inflammatory as well as tolerogenic immune responses. Rapid production by NKT cells of a wide variety of cytokines elicits the downstream activation of both innate and adaptive immune cell subsets such as NK cells, macrophages, dendritic cells, and B cells. These characteristics suggest that NKT cells could play a pivotal early role in shaping developing immune responses. Research in the lab focuses on the investigation of the factors that govern iNKT cell activation and function. We have demonstrated strain-dependent susceptibility to NKT-mediated diseases such as asthma and pregnancy loss is significantly correlated with strain-dependent variability in iNKT cell number and function. Therefore, we are using genetic, molecular, and biochemical techniques to identify factors that modulate iNKT cell function in vivo, and to determine how they affect downstream immune responses.
Last modified December 31 2013 02:09 PM