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

Associate Professor
Pathology & Immunology

Immunology Program
Neurosciences Program

  • 314-362-8452

  • 314-362-8254

  • 314-747-1345

  • 304 McMillan



  • 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.

Mentorship and Commitment to Diversity Statement:
A lack of diversity can be harmful for all of us by potentially perpetuating social injustice and limiting the impact of our work. The Wu lab is committed to diversity, inclusion, and unity. We value individual uniqueness and strive to bring together a diverse team to build a strong, collaborative group. We welcome individuals from all backgrounds.
We aim to foster a positive environment so that each individual can pursue scientific training and knowledge with confidence, creativity, and integrity.

Selected Publications:

Manivasagam S, Williams JL, Vollmer LL, Bollman B, Bartleson JM, Ai S, Wu GF, Klein RS. Targeting IFN-λ Signaling Promotes Recovery from Central Nervous System Autoimmunity. J Immunol. 2022 Feb 18;ji2101041.

Esaulova E, Cantoni C, Shchukina I, Zaitsev K, Bucelli RC, Wu GF, Artyomov MN, Cross AH, and Edelson BT. Single cell RNA-seq analysis of human CSF microglia and myeloid cells in neuroinflammation. Neurology: Neuroimmunology & Neuroinflammation. 2020 May 5;7(4). pii: e732. doi: 10.1212/NXI.0000000000000732.

Parker Harp CR, Archambault AS, Cheung M, Williams JW, Czepielewski RS, Duncker PC, Kilgore AJ, Miller AT, Segal BM, Kim AHJ, Randolph GJ, Wu GF. Neutrophils promote VLA-4-dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation. Proc Natl Acad Sci U S A. 2019;116(48):24221-24230.

Parker Harp CR, Archambault AS, Sim J, Shlomchik MJ, Russell JH, Wu GF. B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis. PLoS One. 2018 Jun 26;13(6):e0199694.

Hoye ML, Archambault AS, Gordon TM, Oetjen LK, Cain MD, Klein RS, Crosby SD, Kim BS, Miller TM, Wu GF. MicroRNA signature of central nervous system-infiltrating dendritic cells in an animal model of multiple sclerosis. Immunology. 2018 May 10.

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.

Last Updated: 3/23/2022 1:37:09 PM

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