JENNIFER GOMMERMAN, Ph.D.

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

Research Focus Areas:

Lymphoid Tissue Microarchitecture 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 how de novo networks between LTbR-expressing support cells and LTab+ activated/memory lymphocytes are established, and the relevance of these networks to the quality of the immune response.

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). Therefore, effective therapies for MS will target these cellular interactions within the CNS itself, and indeed, studying the nature of DC:T cell encounters at sites of inflammation is a relatively new frontier in Immunology. Our preliminary and published data show that the Lymphotoxin (LT) pathway is a critical modulator of DC function, and inhibitors of this pathway prevent EAE relapses. 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.

TNF family members and mucosal immunity

TNF superfamily members also control niches within the mucosal tissues that are important for the generation of IgA such as isolated lymphoid follicles and Peyer's Patches. 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. T 

Lab Members:

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

Recent relevant publications (Sr author or co-Sr author)

1. 1. McCarthy, D.D. *, Kujawa, J. *, McPherson, A.J., McCoy, K.D., Pei, Y., Browning, J.L., Gommerman, J.L.* and Ranger, A*. Mice over-expressing BAFF develop a disease resembling human IgA Nephropathy that is dependent on commensal flora. Manuscript in press at J. Clinicial Investigation
2. 2. 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. PNAS 108:2046, 2011
3. 3. 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
4. 4. Tusche, M., Ward, L.E., Vu, F., McCarthy, D., Gommerman, J.L. * and Mak, T.W. Differential requirement of MALT1 for BAFF-induced outcomes in B cell subsets. J. Exp. Med. 206:2671, 2009
5. 5. Gao, Y., Majchrzak, B., Fish, E.N., and Gommerman, J.L. Dynamic accumulation of plasmacytoid dendritic cells in lymph nodes is regulated by type I Interferon-beta. Blood 114:2623, 200
6. 6. Zaheen, A.*, Boulianne, B.*, Ramachandran, S., Parsa, J-Y., Gommerman, J.L.* and Martin, A.* AID constrains Germinal Center size by Rendering B cells Susceptible to Apoptosis. Blood 114:547, 2009

7. 7. Vu, F., Dianzani, U., Ware, C.F., Mak, T. and Gommerman, J.L. ICOS, CD40 and Lymphotoxin-beta Receptors signal sequentially and inter-dependently to initiate a Germinal Center reaction. J. Immunol. 180:2284, 2008
8. 8. 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

9. 9. McCarthy, D.D^*, Gao, Y-F, Chiu, S., Summers-Deluca, L. and Gommerman, J.L. LIGHT is dispensable for BAFF-mediated hyper-IgA syndrome. Cell. Immunol. 241:85, 2006