Massachusetts General Hospital

My lab 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 have discovered that dendritic cells (DC), cells in charge of presenting antigens and activating T lymphocytes, can additionally “program” T cells 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 a4b7 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. Gastroenterology, in press, 2011; Wang et al. J. Immunol., in press, 2011). In addition, we are exploring the role of lymphocyte trafficking in gut inflammation, intestinal cancer and oral immunological tolerance (Cassani et al., submitted, 2011). 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. 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.
 
See also HMS PhD Programs:

http://www.hms.harvard.edu/dms/immunology/fac/Mora.php

http://www.hms.harvard.edu/dms/bbs/fac/Mora.php

Principal Investigator:

J. Rodrigo Mora, M.D., Ph.D. Assistant Professor of Medicine, Harvard Medical School Assistant Immunologist, Massachusetts General Hospital Co-Director, Immunology Core, Center for the Study of Inflammatory Bowel Disease (CSIBD) Direct Office: (617) 643-4366 Email: jmora3@partners.org or j_rodrigo_mora@hms.harvard.edu Dr. Mora's CV

Faculty/Instructors:

Eduardo J. Villablanca, Ph.D. Lab Phone: (617) 643-4367 Email: evillablanca@partners.org Web Page: www.ejvillablanca.com Dr. Villblanca's CV

 Post-Doctoral Fellows:

Barbara Cassani, Ph.D. Lab Phone: (617) 643-4367 Email: bcassani@partners.org Dr. Cassani's CV
Jaime de Calisto, Ph.D. Lab Phone: (617) 643-4367 Email: jdecalisto@partners.org Dr. de Calisto's CV

 Graduate Students:

Patricia Torregrosa-Paredes, M.S., Karolinska Immunology Ph.D. Program Lab Phone: (617) 643-4367 Email: ptorregrosa-paredes@partners.org Patricia CV
Lindsay Kua, B.A., HMS Immunology Ph.D. Program Lab Phone: (617) 643-4367 Email: lkua@partners.org Lindsay CV
Jeffrey Lian, B.S., HMS Immunology Ph.D. Program Lab Phone: (617) 643-4367 Email: jlian@partners.org Jeffrey CV

Research Technicians:

Allison Cara McNulty, B.Sc. Lab Phone: (617) 643-4367 Email: acmcnulty@partners.org Ms. McNulty CV

Current lines of research in my lab address:
 
• The mechanisms inducing gut-homing T cells, regulatory T cells and IgA-ASC.
• The role of retinoids in gut and systemic immune responses.
• The mechanisms controlling the homing and differentiation of gut-associated dendritic cells.
• The mechanisms regulating immunological tolerance, in particular oral tolerance.
• The role of lymphocyte migration in gut-associated inflammation and cancer.
• The impact of lymphocyte homing modulation in the setting of vaccination.
 
Promoting lymphocyte migration to mucosal tissues might be instrumental in improving vaccination strategies aimed at enhancing immunity in these compartments (e.g., during HIV infection). 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. Thus, I expect that my lab 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.

None at the moment.

Selected Publications:

1. J. Rodrigo Mora, M. Rosa 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) PMID: 12840763
2. J. Rodrigo Mora, Guiying Cheng, Dominic Picarella, Michael Briskin, Natasha Buchanan & Ulrich H. von Andrian. Reciprocal and Dynamic Control of CD8 T Cell Homing by Dendritic Cells from Skin- and Gut-Associated Lymphoid Tissues. J. Exp. Med. 201: 303-316 (2005).
3. J. Rodrigo Mora & Ulrich H. von Andrian. T Cell Homing Diversity and Plasticity: Emerging Platforms for Therapeutic Immunomodulation. Trends Immunol., 27: 235-243 (2006).
4. 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).
5. J. Rodrigo Mora. Homing Imprinting and Immunomodulation in the Gut: Role of Dendritic Cells and Retinoids. Inflamm. Bowel Dis., 14: 275-289 (2008).
6. J. Rodrigo Mora & Ulrich H. Von Andrian. Differentiation and Homing of IgA-Secreting Cells. Mucosal Immunol., 1: 96-109 (2008).
7. Mora JR, von Andrian UH. Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells. Semin Immunol. 2009 Feb;21(1):28-35.
8. Villablanca EJ, Mora JR. A two-step model for Langerhans cell migration to skin-draining LN. Eur J Immunol. 2008 Nov;38(11):2975-80.
9. Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008 Aug 8; 8: 685-698.
10. 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).
    
11. 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) PMID: 21596042.
    
12. 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) PMID: 21646294.
    
13. 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, In press (2011).