Molecular and Genetic Determinants of iNKT Cell Function
Dr. Boyson received his PhD from the University of Wisconsin-Madison in 1997. From 1998 to 2003, he conducted his postdoctoral research at Harvard University in the Department of Molecular and Cellular Biology in the laboratory of Dr. Jack L. Strominger. Dr. Boyson joined the CMB program in 2003.
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.
Borg, Z.D., P. Benoit, G.W.J. Lilley, I.A. Aktan, A.Chant, V.L. DeVault, M. Rincon, and J.E. Boyson. Polymorphisms in the CD1d promoter that regulate CD1d gene expression are associated with impaired NKT cell development. Journal of Immunology 192:189-99.
Klaus, J., Eisenhauer, P., Russo, J., Mason A., Do D., Taatjes, D., Cornillez-Ty, C., Boyson, J.E., Lao L., Zhang, B., Balliff, B. and J. Botten. The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus particles. 2013. Cell Host & Microbe 14(5):522-34.
Huber S.A., Roberts B., Moussawi M., and J.E. Boyson. Slam haplotype 2 promotes NKT but suppresses Vγ4(+) T-cell activation in coxsackievirus B3 infection leading to increased liver damage but reduced myocarditis. 2013. Am J Pathol Feb;182(2):401-9.
Liu W, Moussawi M, Roberts B, Boyson JE, Huber SA. Cross-Regulation of T Regulatory Cell Response after Coxsackievirus B3 Infection by NKT and γδ T Cells in the Mouse. 2013. Am J Pathol. epub ahead of print.
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. 2013. Am J Respir Cell Mol Biol. 48(5):655-64
Nagaleekar, V., G. Sabio, I. Aktan, A. Chant, I.W. Howe, P.J. Benoit, T.M. Thornton, R.J. Davis, M. Rincon, and J.E. Boyson. Translational control of NKT cell cytokine production by p38 MAP kinase. 2011. Journal of Immunology 186(7):4140-4146.
Aktan, I, Chant, AC, Borg, ZD, Damby, DE, Leenstra, PC, Lilley, GWJ, Petty, J, Suratt, BT, Teuscher, C., Wakeland, EK, Poynter, ME, and JE Boyson. Slam haplotypes modulate the response to LPS in vivo through control of NKT cell number and function. 2010. Journal of Immunology 185(1):144-56.
* indicates equal contribution
Borg ZD, Benoit PJ, Lilley GW, Aktan I, Chant A, DeVault VL, Rincon M, Boyson JE (2014) Polymorphisms in the CD1d promoter that regulate CD1d gene expression are associated with impaired NKT cell development. J Immunol 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 (2013) The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus, coronavirus, and filovirus particles. Cell Host Microbe 14(5): 522-34.
Liu W, Moussawi M, Roberts B, Boyson JE, Huber SA (2013) Cross-regulation of T regulatory-cell response after coxsackievirus B3 infection by NKT and γδ T cells in the mouse. Am J Pathol 183(2): 441-9.
Martin RA, Ather JL, Lundblad LK, Suratt BT, Boyson JE, Budd RC, Alcorn JF, Flavell RA, Eisenbarth SC, Poynter ME (2013) 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 48(5): 655-64.
Huber SA, Roberts B, Moussawi M, Boyson JE (2013) Slam haplotype 2 promotes NKT but suppresses Vγ4+ T-cell activation in coxsackievirus B3 infection leading to increased liver damage but reduced myocarditis. Am J Pathol 182(2): 401-9.
Exley MA, Boyson JE (2011) Protective role of regulatory decidual γδ T cells in pregnancy. Clin Immunol 141(3): 236-9.
Ather JL, Ckless K, Martin R, Foley KL, Suratt BT, Boyson JE, Fitzgerald KA, Flavell RA, Eisenbarth SC, Poynter ME (2011) Serum amyloid A activates the NLRP3 inflammasome and promotes Th17 allergic asthma in mice. J Immunol 187(1): 64-73.
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