Biomedical Sciences Graduate Program | University of California, San Francisco

Edward Goetzl, MD
Immunoregulatory G Protein-Coupled Receptors of T-Cells

Selected Publications | Complete Publications

phone	(415) 476-5339
email	edward.goetzl@ucsf.edu
additional websites	Cancer Center Immunology Graduate Program
secondary research affiliation

Dr. Goetzl's laboratory is investigating the expression of vasoactive intestinal peptide (VIP) in T cells and nerves supplying immune organs, as a mechanism for neuroregulation of hypersensitivity reactions. The nanomolar levels of VIP attained at sites of allergic reactions bind to T cell inducible G protein-coupled receptors (VPAC2 Rs) for VIP and signal T cell migration and deviation to a Th2-like phenotype. A T cell-selective VPAC2 GPCR transgenic mouse (TG) has an allergic phenotype, whereas the VPAC2 GPCR knock-out (K/O) mouse has increased delayed-type hypersensitivity, but no detectable allergy. Several carboxyl-terminal deletion mutants of VPAC2 have been identified in T cells that also favor deviation of CD4 T cells to the Th2 phenotype. Current studies are directed to defining the mechanisms of immunoregulation of expression of various types of mutant VPAC2 GPCRs and delineating immune responses of VPAC2 TG x OTII and VPAC2 K/O x OTII mice to oral vs. subcutaneous doses of their preferred peptide antigen.

Dr. Goetzl's laboratory has been elucidating the mechanisms by which the mast cell- and macrophage-derived lipid termed sphingosine 1-phosphate signals through the type 1 (S1P1) and type 4 (S1P4) G protein-coupled receptors to control T cell and B cell migration in tissues, lymphoid system homing, and other immune functions. By applying a range of novel mouse genetic models, functional, antibodies and pharmacological agents, Dr. Goetzl and his colleagues are determining the mechanisms by which the S1P-S1P GPCR axes control immunity normally and in several models of autoimmune diseases.

Selected Publications

Graeler, M., Shankar, G., and Goetzl, E.J. Cutting Edge: Suppression of T cell chemotaxis by sphingosine 1-phosphate. J. Immunol. 169:4084-4087, 2002.

Graeler, M.H., Kong, Y., Karliner, J.S., and Goetzl, E.J., Protein kinase C epsilon-dependence of the recovery from down regulation of S1P 1 G protein-coupled receptors of T lymphocytes. J. Biol. Chem., 2003, vol.278, No. 30, pp.27737-27741

Dorsam, G., Graeler, M, Seroogy, C., Kong, Y., Voice, J., and Goetzl, E.J., Transduction of multiple effectsof sphingosine 1-phosphate on T cell functions by S1P 1 G protein-coupled receptor. J. of Immunology, 2003, 171: 3500-3507

Gräler MH, Goetzl EJ. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G protein-coupled receptors. FASEB J. Express Article - Vol. 18:551-553, March 2004. Full text - 10.1096/fj.03-0910fje.

Graler MH, Huang MC, Watson S, Goetzl EJ. Immunological effects of transgenic constitutive expression of the type 1 sphingosine 1-phosphate receptor by mouse lymphocytes. J Immunol. 2005 Feb 15;174(4):1997-2003.

Rosen H, Goetzl EJ. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol. 2005 Jul;5(7):560-70.

Voice JK, Dorsam G, Lee H, Kong Y, Goetzl EJ. Allergic diathesis in transgenic mice with constitutive T cell expression of inducible vasoactive intestinal peptide receptor. FASEB J. 15:2489-2496, 2001.

Goetzl EJ, Voice JK, Shen S, Dorsam G, Kong Y, West KM, Morrison CF, Harmar AJ. Enhanced delayed-type hypersensitivity and diminished immediate-type hypersensitivity in mice lacking the inducible VPAC2 receptor for vasoactive intestinal peptide. Proc. Natl. Acad. Sci. USA, 98:13854-13859, 2001.

Dorsam, G., and Goetzl, E.J. Vasoactive intestinal peptide receptor-1 (VPAC 1 ) is a novel gene target of the hemolymphopoietic transcription factor Ikaros. J. Biol. Chem. 277:13488-13493, 2001.

Voice J, Donnelly S, Dorsam G, Dolganov G, Paul S, Goetzl EJ. c-Maf and JunB mediation of Th2 differentiation induced by the type 2 G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide. J Immunol. 2004 Jun 15;172(12):7289-96.

Grinninger C, Wang W, Oskoui KB, Voice JK, Goetzl EJ. A natural variant type II G protein-coupled receptor for vasoactive intestinal peptide with altered function. J Biol Chem. 2004 Sep 24; 279(39): 40259-6.

information last updated July 2005