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JENNIFER GOMMERMAN, Ph.D.

 Lymph node architecture, regulation of T cell responses, TNF family members, autoimmunity

Jen Gommerman

 

Department of Immunology
Medical Sciences Building
University of Toronto
Toronto, Ontario M5S 1A8

Tel: (416) 978-6959
Fax: (416) 978-1938
e-mail: jen.gommerman@utoronto.ca










Research Focus Areas:

TNF superfamily members and the Regulation of the Immune Response

Lymphoid microenvironments are specialized niches composed of stromal support cells that are maintained in a differentiated state in order to provide cytokines and chemokines to the lymphocytes that seed them. The Lymphotoxin (LT) pathway is a major player for establishing stromal cell networks in the developing lymph node (LN), the spleen, the gut and the thymus1. LTbR on stromal support cells is constitutively signaled by low levels of LTab expressed on lymphocytes to maintain the integrity of these networks. Although in resting animals this paradigm has been well studied, we know very little about “inducible” networks in the context of immunity where very high levels of LTab are expressed on lymphocytes in a transient manner. My lab is interested in howde novo networks between LTbR-expressing stromal cells and LTab + activated lymphocytes are established, and the relevance of these networks to the quality of the immune response. Furthermore, we are interested in how

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the multiple input signals from TNF superfamily members such as LTbR integrate to promote T cell priming.

The Lymphotoxin Pathway and Multiple Sclerosis

Experimental Autoimmune Encephalomyelitis (EAE), an animal model of Multiple Sclerosis (MS), is induced in susceptible rodent strains by immunization with myelin antigens (Ag). Once primed in the lymph nodes (LN), encephalogenic myelin-specific CD4 T cells acquire the ability to migrate to the central nervous system (CNS), recognize myelin self-Ag and induce inflammation. Within the CNS, protracted inflammation and disease requires the presence of infiltrating T cells that are continually stimulated by Ag presenting cells (APC), in particular dendritic cells (DC). My lab is interested in discerning the mechanism of action of LT pathway inhibitors in relapsing EAE (R-EAE) and will add to our understanding of how encephalogenic T cells are primed by DC within the CNS. Furthermore, we are also interested in how networks of different types of B cells modulate neuro-inflammation.



TNF family members and mucosal immunity

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TNF superfamily members also control niches within the mucosal tissues that are important for the generation of IgA. IgA is important for the regulation of the gut microbiota. We are interested in how TNF family members regulate IgA production and possible novel functions of IgA-secreting plasma cells within the gut. We have also recently shown that IgA-plasma cells generated in the gut can have a consequence on autoimmunity in the periphery in mice that over-express the TNF superfamily member BAFF. How signals through TNF superfamily members modify DC and/or stromal cell function in the gut is a current area of research.







  GommermanLab

Our lab (from left to right):

Jen Gommerman (PI) jen.gommerman@utoronto.ca
Elisa Porfilio (graduate student) elisa.porfilio@utoronto.ca
Natalia Pikor (graduate student) natalia.pikor@utoronto.ca
Thanh Nguyen (undergraduate student) newthanh2003@yahoo.ca
Douglas McCarthy (former PhD graduate) doug.mccarthy@utoronto.ca
Dennis Ng (graduate student) dman.ng@utoronto.ca
Bryant Boulliane (graduate student) bryant.boulianne@utoronto.ca
Lesley Ward (Tech) lesley.ward@utoronto.ca
Jorg Fritz (former PDF, currently faculty at McGill) jorg.fritz@mcgill.ca
Olga Rojas (PDF) olga.rojas@utoronto.ca
Leslie Summers-Deluca (former graduate student) leslie.summersdeluca@utoronto.ca
Georgina Galicia-Rosas (PDF) georgina.galicia@utoronto.ca

RELEVANT PUBLICATIONS (selected)

  • Fritz, J.H., McCarthy, D., Simard, N., Lucia-Rojas, O., Hapfelmeier, S., Rubino, S., Robertson, S.J., Larijani, M., Ivanov, I.I., Martin, A., Casellas, R., Philpott, D.J., E. Girardin, S., McCoy, K.D, Macpherson, A.J., Paige, C.J. and Gommerman, J.L. Acquisition of a multifunctional TNF/iNOS-producing IgA+ plasma cell phenotype in the gut. Nature, 481:199, 2012
  • Summers-Deluca, L., and Gommerman, J.L. Fine-tuning Dendritic Cell Responses by the TNF Superfamily. Nature Reviews Immunology, 2012:12:339
  • McCarthy DD, Kujawa J, Wilson C, Papandile A, Poreci U, Porfilio EA, Ward L, Lawson MA, Macpherson AJ, McCoy KD, Pei Y, Novak L, Lee JY, Julian BA, Novak J, Ranger A, Gommerman JL, Browning JL. Mice over-expressing BAFF develop a disease resembling human IgA Nephropathy that is dependent on commensal flora. J. Clinical Investigation 2011: 121:3991. *Jeff Browning and Jen Gommerman are co-Sr authors having contributed equally.
  • Summers-Deluca, L., Gao, Y., Ng, D., Ward, L.E. and Gommerman, J.L. Dendritic cells integrate CD40 and LTbR-signals to optimize cross-priming of CD8+ T cell responses. Proc. Nat. Acad. Sci. 108:2046, 2011.
  • Summers-Deluca, L., Cosovic, B., McCarthy, D.D., Scheu, S., Pfeffer, K. and Gommerman, J.L. Expression of Lymphotoxin-ab on antigen-specific T cells is required to license dendritic cells in vivo. J. Exp. Med. 204:1071, 2007.
  • Summers-Deluca, L., Pikor, N., O’Leary, J., Galicia-Rosas, G., Ward, L.E., Osborne, L.R. and Gommerman, J.L. Sub-strain differences are the major source of variability in a rodent model of Multiple Sclerosis. J. Immunol. 184:3174, 2010.