Gregory F. Wu, M.D., Ph.D.

Assistant Professor
Neurology
Pathology & Immunology

Immunology Program
Neurosciences Program

  • 314-362-8452

  • 314-362-8254

  • 314-747-1345

  • 8111

  • 304 McMillan

  • wug@neuro.wustl.edu

  • wulab.wustl.edu

  • antigen presentation, dendritic cells, B cells, immunology, intravital microscopy, multiple sclerosis, neurobiology

  • Inflammation and autoimmunity of the central nervous system

Research Abstract:

The main goal of our research is to define the antigen presentation requirements during inflammation within the central nervous system (CNS). Dendritic cells (DCs) are a special class of antigen presenting cell capable of priming nave T cells and initiating a wide spectrum of effector functions. Several lines of evidence suggest that DCs are critical during the pathogenesis of CNS inflammation. This is particularly relevant to diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Research in our lab focuses on the initiation of T cell responses toward myelin antigens and the propagation of encephalitogenic T cell activity during EAE by DCs. We have utilized an in vivo genetic approach for these studies, employing mice that express MHCII only on DCs. We are pursuing three lines of experimentation toward understanding the regulation of T cell function by DCs during autoimmune neuro-inflammation.

During initial studies, we have found that DCs are a minimally sufficient antigen presenting cell (APC) during both the initiation and propagation of neuro-inflammation. What mechanisms do DCs employ in order to perform all APC functions required during EAE? To address this question, we are defining the T cell phenotype based on the signature of T cell receptor (TCR) repertoire usage following EAE induction by DCs alone; characterizing the trafficking and cytokine parameters in vivo for CD4 T cells stimulated by DCs alone; and determining the capacity of DCs to mediate EAE after protein immunization.

Second, we have been actively investigating the anatomic source of DC populations within the CNS that are critical to the propagation of neuro-inflammation. Our results indicate that the radiation-sensitive, bone marrow-derived DC compartment is sufficient for all APC functions during all phases of EAE. Ongoing work in our lab is aimed at elucidating the factors leading to the accumulation of DCs within the CNS during EAE. We are using a candidate approach to define the contribution of specific chemokine receptors and adhesion molecules involved in DC recruitment to the inflamed CNS.

Third, we are evaluating immune cell migration within the CNS during EAE using intravital microscopy. As an initial step, we have examined spinal cord tissue directly ex vivo from diseased mice using 2-photon microscopy. Following induction of EAE in mice we have observed a reticular pattern of fibrous material generated via second harmonics, reminiscent of reticular networks seen within lymphoid organs. We hypothesize that these structures serve as critical anchors for DCs and T cells during cellular interactions within the CNS that contribute to ongoing disease. We plan to study the DC and T cell migrational properties within the CNS in vivo during EAE. In addition, we are devising further methods to track the movement of DCs in vivo during the induction of CNS inflammation.

Selected Publications:

Parker Harp, C.R., Archambault, A.S., Sim, J., Ferris, S.T., Mikesell, R.J., Koni, P.A., Shimoda, M., Linington, C., Russel, J.H., and Wu, G.F. B cell antigen presentation is sufficient to drive neuro-inflammation in an animal model of multiple sclerosis. J Immunol. 2015 Jun 1;194:5077-84.

Wu, G.F., Parker Harp, C.R., and Shindler, K.S. Optic Neuritis: A Model for the Immuno-pathogenesis of Central Nervous System Inflammatory Demyelinating Diseases. Curr Immunol Rev. 2015 August; 11 (2):85-92. Review.

Shin S, Walz KA, Archambault AS, Sim J, Bollman BP, Koenigsknecht-Talboo J, Cross AH, Holtzman DM, Wu GF. Apolipoprotein E Mediation of Neuro-Inflammation in a Murine Model of Multiple Sclerosis. J Neuroimmunol. 2014 Jun; 271(1-2): 8-17.

Barnett LG, Simkins HM, Barnett BE, Korn LL, Johnson AL, Wherry EJ, Wu GF, Laufer, TM. B Cell Antigen Presentation in the Initiation of Follicular Helper T Cell and Germinal Center Differentiation. J Immunol. 2014 Apr; 192(8): 3607-17.

Satake, A, Schmidt, AM, Archambault, AS, Leichner, TM, Wu, GF, Kambayashi T. Differential targeting of IL-2 and T cell receptor signaling pathways selectively expands regulatory T cells while inhibiting conventional T cells.J Autoimmun. 2013 Jul 5.

Archambault, AS, Carrero, JA, Barnett, LG, McGee, NG, Sim, J, Wright, JO, Raabe, T, Chen, P, Ding, H, Allenspach, EJ, Dragatsis, I, Laufer, TM, Wu, GF. Conditional MHCII expression reveals a limited role for B cell antigen presentation
in primary and secondary CD4 T cell responses. J Immunol (cutting edge). 2013 Jul 15;191(2):545-50

Wu, GF, Corbo, E, Schmidt, M, Smith-Garvin, JE, Riese, MJ, Jordan, MS, Laufer, TM, Brown, EJ, Maltzman, JS. Conditional Deletion of SLP-76 in Mature T Cells Abrogates Peripheral Immune Responses. Eur J Immunol. 2011 Jul;41(7):2064-73.

Wu, GF, Shindler, KS, Allenspach, EJ, Stephen, TL, Thomas, HL, Mikesell, RJ, Cross, AH, Laufer, TM. Limited Sufficiency of Antigen Presentation by Dendritic Cells in Models of Central Nervous System Autoimmunity. J Autoimmun. 2011 Feb;36(1):56-64.

Wu GF and Alvarez E. The immunopathophysiology of multiple sclerosis. Neurol Clin. 2011 May;29(2):257-78. (Review).

Last Updated: 9/2/2016 10:33:14 AM

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