Education

Ph.D., Universite Paris, VII, 1996

M.D., Institut Pasteur, Paris, 1991

BPHYS Student

Vu Quoc Dinh, PhD

Megan Borregard

Iva Veseli

Research Summary

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.

This 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.

Overall, 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.

Additional Interests:  T Cell Regulation

Selected Papers

Busque L, Sun M, Buscarlet M, Ayachi S, Feroz Zada Y, Provost S, Bourgoin V, Mollica L, Meisel M, Hinterleitner R, Jabri B, Dubé MP, Tardif JC. High-sensitivity C-reactive protein is associated with clonal hematopoiesis of indeterminate potential. Blood Adv. 2020 06 09; 4(11):2430-2438. 

Kim SM, DeFazio JR, Hyoju SK, Sangani K, Keskey R, Krezalek MA, Khodarev NN, Sangwan N, Christley S, Harris KG, Malik A, Zaborin A, Bouziat R, Ranoa DR, Wiegerinck M, Ernest JD, Shakhsheer BA, Fleming ID, Weichselbaum RR, Antonopoulos DA, Gilbert JA, Barreiro LB, Zaborina O, Jabri B, Alverdy JC. Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity. Nat Commun. 2020 05 11; 11(1):2354. 

Abadie V, Kim SM, Lejeune T, Palanski BA, Ernest JD, Tastet O, Voisine J, Discepolo V, Marietta EV, Hawash MBF, Ciszewski C, Bouziat R, Panigrahi K, Horwath I, Zurenski MA, Lawrence I, Dumaine A, Yotova V, Grenier JC, Murray JA, Khosla C, Barreiro LB, Jabri B. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease. Nature. 2020 02; 578(7796):600-604. 

Zorro MM, Aguirre-Gamboa R, Mayassi T, Ciszewski C, Barisani D, Hu S, Weersma RK, Withoff S, Li Y, Wijmenga C, Jabri B, Jonkers IH. Tissue alarmins and adaptive cytokine induce dynamic and distinct transcriptional responses in tissue-resident intraepithelial cytotoxic T lymphocytes. J Autoimmun. 2020 03; 108:102422. 

Ciszewski C, Discepolo V, Pacis A, Doerr N, Tastet O, Mayassi T, Maglio M, Basheer A, Al-Mawsawi LQ, Green PHR, Auricchio R, Troncone R, Waldmann TA, Azimi N, Tagaya Y, Barreiro LB, Jabri B. Identification of a ?c Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21. Gastroenterology. 2020 02; 158(3):625-637.e13. 

Goel G, Tye-Din JA, Qiao SW, Russell AK, Mayassi T, Ciszewski C, Sarna VK, Wang S, Goldstein KE, Dzuris JL, Williams LJ, Xavier RJ, Lundin KEA, Jabri B, Sollid LM, Anderson RP. Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Sci Adv. 2019 08; 5(8):eaaw7756. 

Caminero A, McCarville JL, Galipeau HJ, Deraison C, Bernier SP, Constante M, Rolland C, Meisel M, Murray JA, Yu XB, Alaedini A, Coombes BK, Bercik P, Southward CM, Ruf W, Jabri B, Chirdo FG, Casqueiro J, Surette MG, Vergnolle N, Verdu EF. Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. Nat Commun. 2019 03 13; 10(1):1198. 

Mayassi T, Ladell K, Gudjonson H, McLaren JE, Shaw DG, Tran MT, Rokicka JJ, Lawrence I, Grenier JC, van Unen V, Ciszewski C, Dimaano M, Sayegh HE, Kumar V, Wijmenga C, Green PHR, Gokhale R, Jericho H, Semrad CE, Guandalini S, Dinner AR, Kupfer SS, Reid HH, Barreiro LB, Rossjohn J, Price DA, Jabri B. Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease. Cell. 2019 02 21; 176(5):967-981.e19. 

Bouziat R, Biering SB, Kouame E, Sangani KA, Kang S, Ernest JD, Varma M, Brown JJ, Urbanek K, Dermody TS, Ng A, Hinterleitner R, Hwang S, Jabri B. Murine Norovirus Infection Induces TH1 Inflammatory Responses to Dietary Antigens. . 2018 11 14; 24(5):677-688.e5. 

Uniken Venema WT, Voskuil MD, Vila AV, van der Vries G, Jansen BH, Jabri B, Faber KN, Dijkstra G, Xavier RJ, Wijmenga C, Graham DB, Weersma RK, Festen EA. Single-Cell RNA Sequencing of Blood and Ileal T Cells From Patients With Crohn's Disease Reveals Tissue-Specific Characteristics and Drug Targets. Gastroenterology. 2019 02; 156(3):812-815.e22. 

Brown JJ, Jabri B, Dermody TS. A viral trigger for celiac disease. PLoS Pathog. 2018 09; 14(9):e1007181. 

Caminero A, Meisel M, Jabri B, Verdu EF. Mechanisms by which gut microorganisms influence food sensitivities. Nat Rev Gastroenterol Hepatol. 2019 01; 16(1):7-18.

Pierre JF, Hinterleitner R, Bouziat R, Hubert N, Leone V, Miyoshi J, Jabri B, Chang EB. Data on changes to mucosal inflammation and the intestinal microbiota following dietary micronutrients in genetically susceptible hosts. Data Brief. 2018 Oct; 20:387-393. 

Nanayakkara M, Lania G, Maglio M, Auricchio R, De Musis C, Discepolo V, Miele E, Jabri B, Troncone R, Auricchio S, Barone MV. P31-43, an undigested gliadin peptide, mimics and enhances the innate immune response to viruses and interferes with endocytic trafficking: a role in celiac disease. Sci Rep. 2018 Jul 17; 8(1):10821. 

Konjar Š, Frising UC, Ferreira C, Hinterleitner R, Mayassi T, Zhang Q, Blankenhaus B, Haberman N, Loo Y, Guedes J, Baptista M, Innocentin S, Stange J, Strathdee D, Jabri B, Veldhoen M. Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes. Sci Immunol. 2018 06 22; 3(24).

Hu MD, Ethridge AD, Lipstein R, Kumar S, Wang Y, Jabri B, Turner JR, Edelblum KL. Epithelial IL-15 Is a Critical Regulator of ?d Intraepithelial Lymphocyte Motility within the Intestinal Mucosa. J Immunol. 2018 07 15; 201(2):747-756. 

Hrdlickova B, Mulder CJ, Malamut G, Meresse B, Platteel M, Kamatani Y, Ricaño-Ponce I, van Wanrooij RLJ, Zorro MM, Jan Bonder M, Gutierrez-Achury J, Cellier C, Zhernakova A, Nijeboer P, Galan P, Withoff S, Lathrop M, Bouma G, Xavier RJ, Jabri B, Bensussan NC, Wijmenga C, Kumar V. A locus at 7p14.3 predisposes to refractory celiac disease progression from celiac disease. Eur J Gastroenterol Hepatol. 2018 08; 30(8):828-837. 

Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado GC, Lira SA, Baier G, Chang EB, Eren AM, Weber CR, Busque L, Godley LA, Verdú EF, Barreiro LB, Jabri B. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature. 2018 05; 557(7706):580-584. View in: PubMed

McDonald BD, Jabri B, Bendelac A. Diverse developmental pathways of intestinal intraepithelial lymphocytes. Nat Rev Immunol. 2018 08; 18(8):514-525. 

Mayassi T, Jabri B. Human intraepithelial lymphocytes. Mucosal Immunol. 2018 09; 11(5):1281-1289. 

Brown JJ, Short SP, Stencel-Baerenwald J, Urbanek K, Pruijssers AJ, McAllister N, Ikizler M, Taylor G, Aravamudhan P, Khomandiak S, Jabri B, Williams CS, Dermody TS. Reovirus-Induced Apoptosis in the Intestine Limits Establishment of Enteric Infection. J Virol. 2018 05 15; 92(10). 

Pierre JF, Hinterleitner R, Bouziat R, Hubert NA, Leone V, Miyoshi J, Jabri B, Chang EB. Dietary antioxidant micronutrients alter mucosal inflammatory risk in a murine model of genetic and microbial susceptibility. J Nutr Biochem. 2018 04; 54:95-104.