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Neuroimmunology Program
Neuroimmunology Laboratory
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Barrow Neurological Institute


Neuroimmunology Laboratory

Barrow Neurological Institute of St. Joseph's Hospital and Medical Center, Phoenix, Arizona
Dr. Fu-Dong Shi, Principal Investigator

Fu-Dong Shi, MD, PhD
Principal Investigator
Director of Neuroimmunology Laboratory and FACS Core

Biographical information

E-mail: fshi@chw.edu

 

Laboratory personnel

Susan Rhodes
Laboratory Coordinator

Mary Price
Flow Cytometry Operator

Ruolan Liu, M.D., PhD
Postdoctoral Research Fellow

Young-Huen Jee, PhD
Postdoctoral Research Fellow

Wenhuan Piao, M.D., PhD
Postdoctoral Research Fellow

 

Laboratory Focus

We have been primarily interested in mechanisms by which NK cells and NKT cells influence the inflammation and autoimmune responses in the central nervous system. We combine cellular immunology and genetic approaches to dissect the role of NK cells and NKT cells in several laboratory models and in human disorders including multiple sclerosis and myasthenia gravis. We conduct preclinical and clinical studies in order to translate the results of this research into novel therapies for neuroinflammatory disorders.


Laboratory Accomplishments

  • Revealed the interleukin 21 receptor/legend pathway in homeostasis of NK cells and CD4+CD25+ regulatory T cells in autoimmune responses to neuroantigens.
  • Defined the suppressor function of NK cells within the central nervous system during experimental autoimmune encephalomyelitis.
  • Discovered the linkage between NKT cells and CD4+CD25+ regulatory T cells in the prevention of autoimmunity.
  • Established and validated several T cell assays in multiple sclerosis patients treated with DNA plasmid and other immune modulatory compounds.


Research Projects

  • Mechanisms of NK cell mediated inhibition of CNS inflammation and autoimmunity.
  • Role of NK cells in the differentiation of myelin reactive TH-17 cells.
  • Effects of cytokine-antibody immune complex on CD4+CD25+ regulatory T cells and the magnitude of autoimmunity.

 

Selected publications

  1. Shi, F. D., H. B. Wang, H. Li, S. Hong, M. Taniguchi, H. Link, L. Van Kaer, and H. G. Ljunggren.  2000.  Natural killer cells determine the outcome of B cell-mediated autoimmunity.  Nat Immunol 1:245-251.
  2. Shi, F. D., K. Takeda, S. Akira, N. Sarvetnick, and H. G. Ljunggren.  2000.  IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-gamma by NK cells.  J Immunol 165:3099-3104.
  3. Shi, F. D., M. Flodstrom, S. H. Kim, S. Pakala, M. Cleary, H. G. Ljunggren, and N. Sarvetnick.  2001.  Control of the autoimmune response by type 2 nitric oxide synthase.  J Immunol 167:3000-3006.
  4. Shi, F. D., M. Flodstrom, B. Balasa, S. H. Kim, K. Van Gunst, J. L. Strominger, S. B. Wilson, and N. Sarvetnick.  2001.  Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse.  Proc Natl Acad Sci U S A 98:6777-6782.
  5. Shi, F., H. G. Ljunggren, and N. Sarvetnick.  2001.  Innate immunity and autoimmunity: from self-protection to self-destruction.  Trends Immunol 22:97-101.
  6. Vollmer, T. L., R. Liu, M. Price, S. Rhodes, A. La Cava, and F. D. Shi.  2005.  Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen.  J Immunol 174:2696-2701.
  7. Liu, R., A. La Cava, X. Bai, Y. Jee, M. Price, D. Campagnolo, P. Christadoss, T.L. Vollmer, L. Van Kaer, and F. D. Shi.  2005.  Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia.  J Immunol 175:7898-7904.
  8. Huang, D*., F.D. Shi*, S. Jung, G.C. Pien, J. Wang, T. P. Salazar-Mather, T. T. He, J. T. Weaver, H.G. Ljunggren, C.A. Biron, D.R. Littman, and R. M. Ransohoff.  2006.  The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system  FASEB J 2006, 20, 896-905.  *co-first author.
  9. Liu, R., L. Van Kaer, A. La Cava, M. Price, S. Rhodes, D. Campagnolo, T. Vollmer, and F.D. Shi.  2006.  Autoreactive T cells mediate NK cell degeneration in autoimmune disease.  J Immunol 2006, 176:5247-5254.
  10. La Cava, A., Van Kaer, L., F.-D. Shi.  2006.  CD4+CD25+ regulatory T cells and NKT cells: regulators regulating regulators.  Trends Immunol 27:322-327.
  11. Shi, F.-D., Van Kaer, L.  2006.  Reciprocal regulation between NK cells and autoreactive T cells.  Nat Rev Immunol 2006, 16:1105-1110.