J. Rodrigo Mora
Assistant Professor of Medicine, Harvard Medical School
Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital
Department of Medicine, Gastrointestinal Unit
55 Fruit Street, GRJ-802
Boston, MA 02114
Lab Members: 2 postdoctoral fellows, 3 graduate students, 1 technician
Visit my lab page here.
Eduardo J. Villablanca, Ph.D., HMS Instructor of Medicine
Jaime De Calisto, Ph.D., HMS Postdoctoral Fellow
Lindsay Kua, Graduate student, HMS Immunology Ph.D. Program
Jeffrey Lian, Graduate student, HMS Immunology Ph.D. Program
Patricia Torregrosa, Visiting Student, Karolinska Immunology Ph.D. Program
Marina Rosengren, B.S., Lab Manager/Technician-I
My laboratory conducts research in the field of Immunology with an emphasis on the gut mucosa and the skin, the largest surfaces exposed to the external environment in the body. We focus on a fundamental immunological aspect, which is to unravel the mechanisms controlling leukocyte trafficking to the gastrointestinal mucosa and the skin, and its implications for protective and pathological immune responses in these compartments.
In order to fulfill their protective or pathogenic functions lymphocytes need to migrate to and enter target tissues throughout the body. This is a complex multi-step process mediated by adhesion receptors expressed both on lymphocytes and the venular endothelium in each tissue. In addition, these adhesion receptors may differ among different organs, thus acting as molecular “zip codes” controlling lymphocyte migration in a tissue-specific fashion, the gut mucosa and the skin being the best paradigms in this regard. We found that dendritic cells (DC) can “program” lymphocytes to migrate in a tissue-specific manner (Nature, 347: 88, 2003). Gut-associated DC (from Peyer’s patches, mesenteric lymph nodes and lamina propria), but not extra-intestinal DC, specifically induce the expression of gut-homing receptors integrin α4β7 and chemokine receptor CCR9 on lymphocytes upon activation, thus endowing T cells with intestinal tropism. Conversely, we showed that skin-derived DC induce skin tropism on T cells and that already committed gut- or skin-tropic T cells exhibit plasticity and therefore can be “re-educated” to change their migratory potential (J. Exp. Med, 201: 303, 2005). We also demonstrated that B cells and IgA antibody-secreting cells (IgA-ASC) can be imprinted with gut-tropism by gut-associated DC via a mechanism dependent on the vitamin A metabolite all-trans retinoic acid (RA) and that the mechanisms imprinting gut-homing lymphocytes are conserved between mice and humans (Science, 314: 1157, 2006). Thus, gut-associated DC and RA shape gut mucosal immunity by modulating lymphocyte migration and the generation of gut-tropic IgA-ASC.
Current work in my laboratory addresses how gut-associated DC are “educated” in the gut to acquire their capacity to produce RA and imprint gut-tropism and IgA antibody-secreting capacity on lymphocytes (Villablanca et al. 2011, Gastroenterology, 141: 176; Wang et al. 2011, J. Immunol., 187: 141). In addition, we are exploring the role of lymphocyte trafficking in gut inflammation, intestinal cancer and oral immunological tolerance (Cassani et al., 2011, Gastroenterology, 141: 2109). Our work may also have clinical implications since DC are increasingly being used as therapeutic vehicles for vaccination. Moreover, interfering with the mechanisms inducing lymphocyte migration to the gut mucosa or the skin can be a very effective and specific therapeutic approach in autoimmune conditions affecting these compartments (reviewed in Villablanca et al. 2011, Gastroenterology, 140: 1776). Thus, I expect that research in my laboratory will provide new insights into the mechanisms regulating the migration of lymphocytes under normal and pathological conditions, with the possibility of suggesting new therapeutic avenues.
Current lines of research in my laboratory:
i) Mechanisms inducing gut-homing T cells, regulatory T cells and IgA-ASC.
ii) Role of retinoids in gut and systemic immune responses.
iii) Mechanisms controlling homing and differentiation of gut-associated dendritic cells.
iv) Mechanisms regulating immunological tolerance, in particular oral tolerance.
v) Role of lymphocyte migration in gut-associated inflammation and cancer.
vi) Impact of lymphocyte homing modulation in the setting of vaccination.
Barbara Cassani, Eduardo J. Villablanca, Francisco J. Quintana, Paul E. Love, Adam Lacy-Hulbert, William S. Blaner, Tim Sparwasser, Scott B. Snapper, Howard L. Weiner & J. Rodrigo Mora. Gut-tropic T cells expressing Integrin α4β7 and CCR9 are Required for Induction of Oral Immune Tolerance in Mice. Gastroenterology, 141: 2109-2118 (2011)
Sen Wang, Eduardo J. Villablanca, Jaime De Calisto, Daniel C. Gomes, Deanna D. Nguyen, Emiko Mizoguchi, Jonathan C. Kagan, Hans-Christian Reinecker, Nir Hacohen, Cathryn Nagler, Ramnik J. Xavier, Bartira Rossi-Bergmann, Yi-Bin Chen, Rune Blomhoff, Scott B. Snapper & J. Rodrigo Mora. MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. J. Immunol., 187: 141-150 (2011)
Eduardo J. Villablanca, Sen Wang, Jaime De Calisto, Daniel C. Gomes, Maureen A. Kane, William Blaner, Joseph L. Napoli, William S. Blaner, Yi-Bin Chen, Rune Blomhoff, Hiroyuki Kagechika, Mario Rosemblatt, Maria Rosa Bono, Ulrich H. von Andrian & J. Rodrigo Mora. MyD88 and Retinoic Acid Signaling Pathways Interact to Modulate Gastrointestinal Activities of Dendritic Cells. Gastroenterology, 141: 176-185 (2011)
Eduardo J. Villablanca, Barbara Cassani, Ulrich H. von Andrian & J. Rodrigo Mora. Targeting gut-homing receptors as a therapeutic platform in IBD. Gastroenterology, 140: 1776-1784 (2011)
J. Rodrigo Mora, Makoto Iwata, Bertus Eksteen, Si-Young Song, Tobias Junt, Balimkiz Senman, Kevin L. Otipoby, Aya Yokota, Hajime Takeuchi, Paola Ricciardi-Castagnoli, Klaus Rajewsky, David H. Adams & Ulrich H. von Andrian. Generation of gut-homing IgA-secreting cells by intestinal dendritic cells. Science, 314: 1157-1160 (2006)
J. Rodrigo Mora, María R. Bono, N. Manjunath, Wolfgang Weninger, Lois Cavanagh, Mario Rosemblatt & Ulrich H. von Andrian. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature. 424: 88-93 (2003)
Last Update: 1/3/2013