Department of Medicine
Cancer Research Center
Committee on Immunology
Committee on Molecular Metabolism
Ph.D., Universite Paris, VII, 1996
M.D., Institut Pasteur, Paris, 1991
Phone: (773) 834-8670
The University of Chicago
900 East 57th Street
Chicago, Illinois 60637
Related Research Interests:
Bana Jabri, M.D., Ph.D.
of Memory/Effector T Cell Mediated Immune Respones in Normal and
Diseased Conditions; Interface Between Innate and Adaptive Immunity.
To face multiple environmental aggressions from pathogens and dietary
elements, the intestinal mucosa is colonized by an army of mobile
antigen-specific effector T lymphocytes and by a distinct population of
resident T cells involved in the tissue stress response. The intestine
is in fact the only mammalian site allowing ready access to the
effector phase of immune responses in the tissue microenvironment.
We study a family of surface
receptors called NKG2 that are differentially expressed by subsets of
intestinal T cells and regulate the signaling threshold of the T cell
antigen receptor through the recruitment of tyrosine phosphatase and
kinase. The NKG2 ligands are MHC-I like molecules induced by intestinal
epithelial cells upon stress and inflammation. The NKG2 receptors
expressed by T cells are themselves regulated by two opposing cytokines
IL-15 and TGF secreted by epithelial cells.
complex system, which ensures the fine-tuning of immune responses by
the tissue environment itself, appears to be dysregulated in autoimmune
and cancer conditions. A second line of study in the laboratory focuses
on an intestinal disease associated with such a dysregulation of the
NKG2 system, celiac disease. Celiac disease is provoked by intestinal
exposure to a well known dietary antigen, gliadin, in humans expressing
the HLA-DQ2 or DQ8 molecules. Using HLA/gliadin tetramers to physically
identify the effector T cells in humans and in humanized mouse models,
we are dissecting the sequence of events leading to the destruction of
intestinal epithelial cells.
we use a range of molecular and cellular approaches, including the
study of signal transduction, cellular immunology and genetic
engineering of mouse models, to study the developmental and functional
aspects of immune function in the mouse and human intestine. These
studies address basic immunological questions and may lead to novel
insights into the mechanisms of inflammatory intestinal diseases.
Park, SH., Guy-Grand, D., Lemonnier, FA., Wang, CR, Bendelac, A., Jabri, B. Selection and expansion of CD8aa+TCRab+ intestinal intraepithelial lymphocytes in the absence of both classical MHC class I and non classical CD1 molecules. J Exp Med; 190:885-890. 1999.
Green, HR, Jabri, B. Coeliac disease. Lancet, 362: 383-391. 2003.
Meresse, B., Chen, Z, Ciszewski, C., Tretiakova, M., Bhagat, G., Krausz, T.N., Raulet, D.H., Lanier, L.L., Groh, V., Spies, T., Ebert, E.C., Green, P.H., Jabri, B. Coordinated inducation by IL-15 of a TCR-independent, NKG2D signaling pathway converts CTLs into natural killer-like, lymphokine activated killer (LAK) cells in celiac disease. Immunity, 21:357-366. 2004.
Marketon, M.M., Depaolo, R.W., Debord, K.L., Jabri, B, Schneewind, O. Type III injection of select immune cells during plague infections. Science, 309:1739-41. 2005.
Meresse, B. Curran, S.A., Ciszewski, C., Orbelyan, G., Setty, M., Bhagat, G., Lee, L., Tretiakova, M., Semrad, C., Kistner, E., Winchester, R.J., Braud, V., Lanier, L.L., Geraghty, D., Green, P.H., Guandalini, S. and Jabri, B. Reprogramming of CTLs into natural killer–like cells in celiac disease. Journal of Experimental Medicine, 203:1345-55, 2006.
Fujiya, M., Musch, M.W., Nakagawa, Y., Hu, S., Alverdy, J., Kohgo, Y., Schneewind, O., Jabri, B., Chang, E.B.. Quorum sensing CSF of B.subtilis, through OCTN2 transport, contributes to intestinal homeostasis. Cell Host and Microbe, 1:299-309, 2007.
Siegel, M., Strnad, P., Watts, R.E., Choi ,K., Jabri, B., Omary, M.B., Khosla, C.. Extracellular transglutaminase 2 is catalytically inactive, but is transiently activated upon tissue injury. PLoS ONE 3(3): e1861 doi:10.1371, 2008.
DePaolo RW, Tang F, Kim I, Han M, Levin N, Ciletti N, Anderson DM, Schneewind O and Bana Jabri. 2008. TLR6 drives differentiation of tolerogenic DC and contributes to LcrV-mediated plague pathogenesis. Cell Host & Microbe, 16:350-61, 2008.
Hovhannisyan, Z., Angela Weiss, A,, Martin, A., Wiesner, M., Tollefsen, S., Yoshida, K., Ciszewski, C., Curran, SA, Murray, JA, David, CS, Sollid, LM,4, Koning, F., Teyton, L., and Jabri, B.. Multiple impacts of HLA-DQ8 b57 polymorphism on the anti-gluten T cell response in celiac disease. Nature, 27;534-8, 2008.
Tang, F., Chen, Z., Ciszewski, C., Setty, M., Solus, J., Tretiakova, M., Ebert, E., Han, J., Lin, A., Guandalini, S., Groh, V., Spies, T., Green, P. and Jabri, B.. Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15. J Exp. Med., 206:707-19, 2009.
Hanaoka, N., Jabri, B., Dai, Z., Ciszewski, C., Stevens, A.M., Yee, C., Nakakuma, H., Spies, T., Groh, V.. NKG2D initiates caspase-medicated CD3 degradation and lymphocyte receptor impairments associated with human cancer and autoimmune disease. J. of Immunol., 185:5732-42. 2010. PMID: 20926796. PMCID in process.
Abadie V, Sollid LM, Barreiro LB, Jabri B, Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu Rev Immunol. 2011 Apr 23;29:493-525.
DePaolo, R.W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J.A., Wang, W., Marietta, E.V., Kasarda, D.D. Waldmann, T.A., Murray, J.A., Semrad, C., Kupfer, S. Belkaid, Y., Guandalini, S., Jabri. B.. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature, 471:220-224. 2011.
Faculty and Research