Current and Past Areas of Interest
Isolation of a dimeric form of IL-2 in murine tissues
Disturbed blood flow and inflammation remain critical components of the development of vascular disease, yet how disturbed flow translates into inflammation is not well defined. The findings in this paper suggest that IL-2 represents another avenue of investigation with respect to this connection. Our findings are supported by previous studies in the mid 90’s from the Michal Schwartz lab, demonstrating the discovery of a cytotoxic, dimeric form of IL-2 in fish optic neurons.
Wrenshall LE, Clabaugh SE, Cool DR, Arumugam P, Grunwald WC, Smith DR, Liu GC, Miller JD.
Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues. PLoS One. 2014 Jul 14;9(7):e102191.
Association of IL-2 with heparan sulfate
IL-2 plays a major role in the up and down regulation of immune responses. Consequently, the availability of IL-2 has a major impact on immune responses. My laboratory determined that IL-2 is retained in multiple tissues by heparan sulfate, and that functional IL-2 is released by heparanase digestion. We also determined that heparan-sulfate bound IL-2 is a major contributor to antigen-specific immune responses.
vessels and released in biologically active form by heparanase. Immunol and Cell Biol 2012 Feb;90(2):159-67.
proteoglycan in murine spleen. Immunol and Cell Biol, 2008 Feb; 86(2): 192-9. Epub 2007 Nov 27.
specific immune responses by heparan-sulfate-bound IL-2. J Immunol, 2003 Jun; 170(11): 5470-4.
Immunol, 1999; 163: 3793.
IL-2 plays a major role in the up and down regulation of immune responses. Consequently, the availability of IL-2 has a major impact on immune responses. My laboratory determined that IL-2 is retained in multiple tissues by heparan sulfate, and that functional IL-2 is released by heparanase digestion. We also determined that heparan-sulfate bound IL-2 is a major contributor to antigen-specific immune responses.
vessels and released in biologically active form by heparanase. Immunol and Cell Biol 2012 Feb;90(2):159-67.
proteoglycan in murine spleen. Immunol and Cell Biol, 2008 Feb; 86(2): 192-9. Epub 2007 Nov 27.
specific immune responses by heparan-sulfate-bound IL-2. J Immunol, 2003 Jun; 170(11): 5470-4.
Immunol, 1999; 163: 3793.
Contribution of IL-2 to thymic development and B cell tolerance
Studies on the contribution of IL-2 to the development of the thymus have led to conflicting results. My
studies determined that this controversy was likely due to the presence of IL-2 in IL-2 knockout mice,
since they are nearly always born from IL-2 heterozygous mothers. These studies determined that (1)
IL-2 does impact thymic development, and (2) IL-2 knockout mice have IL-2 producing cells, which can
yield misleading results. My laboratory also determined how IL-2 deficiency impacts B cell tolerance.
presence of interleukin-2 in interleukin-2 knock out mice: implications for the role of interleukin-2 in
thymic function. Cell Immunol, 2007 Feb; 245(2): 80-90. Epub 2007 May 23.
generation of autoimmune B cells. J Autoimmun, 2007 Sep-Nov; 29(2-3): 125-33. Epub 2007 Aug 9
Studies on the contribution of IL-2 to the development of the thymus have led to conflicting results. My
studies determined that this controversy was likely due to the presence of IL-2 in IL-2 knockout mice,
since they are nearly always born from IL-2 heterozygous mothers. These studies determined that (1)
IL-2 does impact thymic development, and (2) IL-2 knockout mice have IL-2 producing cells, which can
yield misleading results. My laboratory also determined how IL-2 deficiency impacts B cell tolerance.
presence of interleukin-2 in interleukin-2 knock out mice: implications for the role of interleukin-2 in
thymic function. Cell Immunol, 2007 Feb; 245(2): 80-90. Epub 2007 May 23.
generation of autoimmune B cells. J Autoimmun, 2007 Sep-Nov; 29(2-3): 125-33. Epub 2007 Aug 9
Heparan sulfate glycosaminoglycan impacts immune function
Historically, the extracellular matrix was considered to be an inert “glue” holding cells together to form an organ. The extracellular matrix is now known to impact cell function, and cells impact the composition of the extracellular matrix. My studies, demonstrating that heparan sulfate impacts several aspects of immune responses, contributed to this knowledge.
J Leuk Biol, 1999 Sep; 66(3): 391.
macrophages leading to divergent biological outcomes. J Immunol, 1995; 154(2): 871.
Transplantation, 1994; 57(7): 1087.
the ontogenic expression of TcR, CD4, and CD8. Human Immunology, 1993 November; 38(8): 165.
Historically, the extracellular matrix was considered to be an inert “glue” holding cells together to form an organ. The extracellular matrix is now known to impact cell function, and cells impact the composition of the extracellular matrix. My studies, demonstrating that heparan sulfate impacts several aspects of immune responses, contributed to this knowledge.
J Leuk Biol, 1999 Sep; 66(3): 391.
macrophages leading to divergent biological outcomes. J Immunol, 1995; 154(2): 871.
Transplantation, 1994; 57(7): 1087.
the ontogenic expression of TcR, CD4, and CD8. Human Immunology, 1993 November; 38(8): 165.