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.
Ather JL, Foley KL, Suratt BT, Boyson JE, Poynter ME. Airway epithelial NF-kB activation promotes the ability to overcome inhalational antigen tolerance. Clin Exp Allergy. 2015 Jan 23. doi: 10.1111/cea.12491. [Epub ahead of print]
Borg ZD, Benoit PJ, Lilley GW, Aktan I, Chant A, DeVault VL, Rincon M, Boyson JE. Polymorphisms in the CD1d promoter that regulate CD1d gene expression are associated with impaired NKT cell development. J Immunol. 2014 Jan 1;192(1):189-99.
Klaus JP, Eisenhauer P, Russo J, Mason AB, Do D, King B, Taatjes D, Cornillez-Ty C, Boyson JE, Thali M, Zheng C, Liao L, Yates JR 3rd, Zhang B, Ballif BA, Botten JW. The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus, coronavirus, and filovirus particles. Cell Host Microbe. 2013 Nov 13;14(5):522-34.
Liu W, Moussawi M, Roberts B, Boyson JE, Huber SA. Cross-Regulation of T Regulatory Cell Response after Coxsackievirus B3 Infection by NKT and ?d T Cells in the Mouse. Am J Pathol. 2013 Aug;183(2):441-9.
Martin RA, Ather JL, Lundblad LK, Suratt BT, Boyson JE, Budd RC, Alcorn JF, Flavell RA, Eisenbarth SC, Poynter ME. Interleukin-1 receptor and caspase-1 are required for the Th17 response in nitrogen dioxide-promoted allergic airway disease. Am J Respir Cell Mol Biol. 2013 May;48(5):655-64.
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., Boyson J.E.. Protective role of regulatory decidual gd T cells in pregnancy. Clin Immunol 2011;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. Serum Amyloid A Activates the NLRP3 Inflammasome and Promotes Th17 Allergic Asthma in Mice. J Immunol 2011;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. J Immunol 2011;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. Am J Respir Cell Mol Biol. 2011;44(1):11-23.
Publications in Pubmed