Research InterestsAdaptive Immunity, Autoimmunity, Gut Immunology, Multiple Sclerosis
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Autoimmune diseases such as Multiple Sclerosis (MS) pose an enormous burden on our Canadian society. For reasons that are unclear, such diseases are on the rise. Moreover, therapies for these diseases remain relatively non-specific, targeting large arms of the immune system. Some forms of autoimmunity, such as progressive MS, have no effective treatments. My lab is focused on (1) mechanisms of immune dysregulation in autoimmune disease, particularly MS; (2) understanding the reason for the rapid increase in autoimmune disease observed in Canada and (3) determining the role of TNF family members in immune cell biology.
We enjoy the benefits of a collaborative team representing a diverse skill ideal for study of human and mouse model systems. Our weekly lab meetings and journal clubs, as well as social outings such as an annual canoe trip, facilitate effective team-work and an enjoyable work atmosphere.
From top left to bottom right: Jennifer Yam (MSc candidate), Evelyn Lau (Undergraduate student), Dennis Lee (PhD candidate), Blandine Maitre (Research Associate), Elisa Porfilio (PhD candidate), Georgina Galicia (Post-Doctoral Fellow), Natalia Pikor (Post-Doctoral Fellow), Lesley Ward (Technician), Leslie Leung (MSc candidate), Conglei Li (Post-Doctoral Fellow), Tian Sun (PhD candidate), Olga Rojas (Post- Doctoral Fellow), Jen Gommerman (PI).
Dysregulation of immune cell function in autoimmunity
MS is a complex disease with no known cause or cure. Based on genetic and pathology data, we know that the immune system plays a very important role in this disease. My lab is interested in how immune cells become activated with the CNS environment. In particular, using an animal model of MS (Experimental Autoimmune Encephalomyelitis), we have been studying immune cell rich structures found in the meninges. In addition, Immunologists have learned that B-lymphocytes play a very important role in modulating autoimmunity. In collaboration with a multi-disciplinary team of neuroimmunologists and using a number of animal and human model systems, we are currently exploring how pro- and anti- inflammatory B cells impact MS pathogenesis. Lastly, we are particularly interested in how the mucosal immune system in the gut influences autoimmune responses in the CNS. This work is supported by the MS Society of Canada (single PI grant) and the MS Society Research Foundation of Canada (team grant with Drs. Amit Bar-Or and Alexandre Prat).
Why are autoimmune disease on the rise in Canada?
The highest prevalence of chronic inflammatory diseases is found in northern latitude countries where a 3- 5-fold incidence increase has been observed over the last 30-50 years. Such a rapid rise in disease can only be explained by environmental changes, the nature of which remains unknown. We have focused on the gut microbiome as a possible modifier of disease risk in genetically susceptible individuals. The gut microbiome is one of the most densely populated bacterial communities, and, in the gut, interactions between the microbiome and the host immune system are played out across a thin barrier comprised of epithelial cells. Using a combination of animal models and human tissues, we are examining interactions between the microbiome and the mucosal immune system, in particular mucosal B lineage cells such as IgA+ plasma cells. We are exploring how this large reservoir of IgA+ plasma cells reflects ongoing responses to the microbiome and what role IgA+ plasma cells may play in inflammatory responses. This work is supported by Canadian Institutes of Health Research Research (single PI grant) and the Connaught Foundation (team grant, JG as principal PI).
TNF family members and immune cell biology
TNF family members play diverse roles in the immune system, and therapies for treatment of some autoimmune disease are targeted at TNF family members. We have a long-standing interest in both the Lymphtooxin and BAFF pathways in the context of chronic inflammatory conditions. Using a combination of animal models and human systems, we are interrogating the role of these pathways in a variety of immune contexts including mucosal IgA responses, germinal centre reactions and Dendritic Cell biology. This work is supported by Canadian Institutes of Health Research Research (single PI grant) and the Kidney Foundation (single PI grant).
Publications and Awards
- Gommerman JL, Rojas OL, Fritz JH. Re-thinking the functions of IgA(+) plasma cells. Gut Microbes. 2014;5(5):652-62.
- Boulianne B, Le MX, Ward LA, Meng L, Haddad D, Li C, Martin A, Gommerman JL. AID-expressing germinal center B cells cluster normally within lymph node follicles in the absence of FDC-M1+ CD35+ follicular dendritic cells but dissipate prematurely. J Immunol. 2013;191(9):4521-30.
- Galicia, G, Boulianne, B, Pikor, N, Martin, A, Gommerman, JL. Secondary B cell receptor diversification is necessary for T cell mediated neuro-inflammation during experimental autoimmune encephalomyelitis. PLoS One. 2013;22(8):e61478.
- Fritz JH, Lucia-Rojas O, Simard N, McCarthy D, Hapfelmeier S, Rubino S, Robertson SJ, Larijani M, Ivanov II, Martin A, Casellas R, Philpott DJ, Girardin S, McCoy KD, Macpherson AJ, Paige CJ and Gommerman JL. Acquisition of a multifunctional TNF/iNOS-producing IgA+ plasma cell phenotype in the gut. Nature. 481:199, 2012.
- Summers-Deluca L and Gommerman JL. Fine-tuning dendritic cell biology by the TNF superfamily. Nat Rev Immunol. 12:339, 2012.
- 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 overexpressing BAFF develop a disease resembling human IgA Nephropathy that is dependent on commensal flora. J. Clinical Investigation. 121:3991, 2011
- Summers-Deluca L, Gao Y, Ng D, Ward LE and Gommerman JL. Dendritic cells integrate CD40 and LTβR-signals to optimize cross-priming of CD8+ T cell responses. Proc. Nat. Acad. Sci. 108:2046, 2011.
- Summers-Deluca L, Pikor N, O’Leary J, Galicia-Rosas G, Ward LE, Osborne LR and Gommerman JL. Sub-strain differences are the major source of variability in a rodent model of Multiple Sclerosis. J. Immunol. 184:3174, 2010.
- Vu F, Dianzani U, Ware CF, Mak T and Gommerman JL. ICOS, CD40 and Lymphotoxin-beta Receptors signal sequentially and inter-dependently to initiate a Germinal Center reaction. J. Immunol. 180:2284, 2008.
- Summers-Deluca L, Cosovic B, McCarthy DD, Scheu S, Pfeffer K and Gommerman JL. Expression of Lymphotoxin-αβ on antigen-specific T cells is required to license dendritic cells in vivo. J. Exp. Med. 204:1071, 2007.