Semi-invariant NKT (iNKT) cells comprise an unusual 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. Research in the lab focuses on the investigation of the factors that govern iNKT cell activation and function.
Project 1: Molecular Determinants of iNKT Cell Activation by CD1d and its Ligands. We are interested in examining the nature of the interaction of the semi-invariant TCR with glycolipid ligands bound by CD1d. We are using site-directed mutagenesis to systematically identify TCR residues fundamentally important in CD1d/ligand recognition. To gain insight into the diversity and the identity of cellular endogenous CD1d ligands we are also examining the glycolipid biosynthetic pathway of CD1d-expressing cells. We use pharmacological inhibitors as well as siRNAs to inhibit the production of certain glycolipids in CD1d-expressing cells. This approach, in conjunction with the mapping of the TCR interaction site will allow us to better understand the rules governing iNKT cell activation and subsequent function.
Project 2: Determinants of iNKT Cell Activation and Function in vivo. Because iNKT cells can affect such a wide variety of immune responses, variability in their function can have significant physiological effects. For example, 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 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, such as NK and B cell activation.
Huber SA, Roberts B, Moussawi M, Boyson JE. Slam haplotype 2 promotes NKT but suppresses v?4(+) T-cell activation in coxsackievirus b3 infection leading to increased liver damage but reduced myocarditis. Am J Pathol. 2013;182(2):401-9.
Exley, M.A. and J.E. Boyson. 2011. Protective role of regulatory decidual gd T cells in pregnancy. Clinical Immunology 141:236–239.
Ather, J.L., K. Ckless, R. Martin, K.L. Foley, B.T. Suratt, J.E. Boyson, K.A. Fitzgerald, R A. Flavell, S.C. Eisenbarth, and M.E. Poynter. 2011. Serum Amyloid A Activates the NLRP3 Inflammasome and Promotes Th17 Allergic Asthma in Mice. Journal of Immunology 187(1): 64-73.
Nagaleekar V, Sabio G, Aktan I, Chant A, Howe IW, Thornton TM, Beniot PJ, Davis RJ, Rincon M, Boyson JE. Regulation of NKT cell cytokine production in NKT cells by p38 MAP kinase. 2011. Journal of Immunology 186(7):4140-4146.
Paveglio S, Allard J, Foster S, Ather J, Bevelander M, Mayette J, Whittaker L, Boyson JE, Poynter ME. Airway epithelial indoleamine 2,3, -dioxygenase inhibits CD4+ T cells during Aspergillus fumigatus antigen exposure. 2011. Am J Respir Cell Mol Biol. 44(1):11-23.
Hodgkins SR, Ather JL, Paveglio SA, Allard JL, Whittaker LeClair LA, Suratt BT, Boyson JE, Poynter ME. NO2 Inhalation Induces Maturation of Pulmonary CD11c+ Cells that Promote Antigen-Specific CD4+ T Cell Polarization. 2010. Respiratory Research 11(1): 102.
Aktan IA, Chant A, Borg ZD, Damby DE, Leenstra PC, Lilley GWJ, Petty J, Suratt BT, Teuscher C, Wakeland EK, Poynter ME, Boyson JE. Slam haplotypes modulate the response to LPS in vivo through control of NKT cell number and function. Journal of Immunology 185, 144 -156; 2010.
Olson CM, Bates TC, Izadi H, Radolf JD, Huber SA, Boyson JE, Anguita J. Local production of interferon gamma by invariant natural killer T cells modulates acute Lyme carditis. Journal of Immunology 182(6): p. 3728-3734; 2009.
Exley MA, Hou R, Shaulov A, Tonti E, Dellabona P, Casorati G, Akbari O, Akman HO, Greenfield EA, Gumperz JE, Boyson JE, Balk SP, Wilson SB. Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop. European Journal of Immunology 38(6):1756-1766; 2008.
Rymarchyk SL, Lowenstein H, Mayette J, Foster SR, Damby D, Howe IW, Aktan I, Meyer RE, Poynter ME, Boyson JE. Widespread natural variation in NKT cell number and function. Immunology 125:331-343; 2008.
Boyson JE, Nagarkatti N, Nizam L, Exley MA, Strominger JL. Gestation stage-dependent mechanisms of iNKT cell-mediated pregnancy loss. Proceedings of the National Academy of Sciences USA 103(12):4580-4585; 2006.
Complete List of Publications
