Bana Jabri

University of Illinois at Chicago, Chicago, Illinois, United States

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Publications (71)839.37 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Isotretinoin, a vitamin A analogue, can promote a pro-inflammatory milieu in the small intestine in response to dietary antigens. We hypothesized that oral isotretinoin exposure would increase the risk of celiac disease (CD).
    American Journal of Clinical Dermatology 07/2014; · 1.84 Impact Factor
  • Valérie Abadie, Bana Jabri
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    ABSTRACT: Interleukin-15 (IL-15) exerts many biological functions essential for the maintenance and function of multiple cell types. Although its expression is tightly regulated, IL-15 upregulation has been reported in many organ-specific autoimmune disorders. In celiac disease, an intestinal inflammatory disorder driven by gluten exposure, the upregulation of IL-15 expression in the intestinal mucosa has become a hallmark of the disease. Interestingly, because it is overexpressed both in the gut epithelium and in the lamina propria, IL-15 acts on distinct cell types and impacts distinct immune components and pathways to disrupt intestinal immune homeostasis. In this article, we review our current knowledge of the multifaceted roles of IL-15 with regard to the main immunological processes involved in the pathogenesis of celiac disease.
    Immunological Reviews 07/2014; 260(1):221-34. · 12.16 Impact Factor
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    ABSTRACT: The NKG2 family of NK receptors includes activating and inhibitory members. With the exception of the homodimer-forming NKG2D, NKG2 receptors recognize the nonclassical MHC class I molecule HLA-E, and they can be subdivided into two groups: those that associate with and signal through DAP12 to activate cells, and those that contain an ITIM motif to promote inhibition. The function of NKG2 family member NKG2E is unclear in humans, and its surface expression has never been conclusively established, largely because there is no Ab that binds specifically to NKG2E. Seeking to determine a role for this molecule, we chose to investigate its expression and ability to form complexes with intracellular signaling molecules. We found that NKG2E was capable of associating with CD94 and DAP12 but that the complex was retained intracellularly at the endoplasmic reticulum instead of being expressed on cell surfaces, and that this localization was dependent on a sequence of hydrophobic amino acids in the extracellular domain of NKG2E. Because this particular sequence has emerged and been conserved selectively among higher order primates evolutionarily, this observation raises the intriguing possibility that NKG2E may function as an intracellular protein.
    Journal of immunology (Baltimore, Md. : 1950). 06/2014;
  • Bana Jabri, Xi Chen, Ludvig M Sollid
    Nature Structural & Molecular Biology 04/2014; · 11.90 Impact Factor
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    ABSTRACT: Antibiotic resistance among highly pathogenic strains of bacteria and fungi is a growing concern in the face of the ability to sustain life during critical illness with advancing medical interventions. The longer patients remain critically ill, the more likely they are to become colonized by multidrug-resistant (MDR) pathogens. The human gastrointestinal tract is the primary site of colonization of many MDR pathogens and is a major source of life-threatening infections due to these microorganisms. Eradication measures to sterilize the gut are difficult if not impossible and carry the risk of further antibiotic resistance. Here, we present a strategy to contain rather than eliminate MDR pathogens by using an agent that interferes with the ability of colonizing pathogens to express virulence in response to host-derived and local environmental factors. The antivirulence agent is a phosphorylated triblock high-molecular-weight polymer (here termed Pi-PEG 15–20) that exploits the known properties of phosphate (Pi) and polyethylene glycol 15-20 (PEG 15-20) to suppress microbial virulence and protect the integrity of the intestinal epithelium. The compound is nonmicrobiocidal and appears to be highly effective when tested both in vitro and in vivo. Structure functional analyses suggest that the hydrophobic bis-aromatic moiety at the polymer center is of particular importance to the biological function of Pi-PEG 15-20, beyond its phosphate content. Animal studies demonstrate that Pi-PEG prevents mortality in mice inoculated with multiple highly virulent pathogenic organisms from hospitalized patients in association with preservation of the core microbiome. FOOTNOTES Received 7 October 2013. Accepted 17 November 2013. Address correspondence to John C. Alverdy, jalverdy{at}surgery.bsd.uchicago.edu, or Olga Zaborina, ozaborin{at}surgery.bsd.uchicago.edu. O.Z. and J.C.A. are senior coauthors for this paper. Published ahead of print 25 November 2013 Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.02183-13. Copyright © 2014, American Society for Microbiology. All Rights Reserved. The authors have paid a fee to allow immediate free access to this article.
    Antimicrobial Agents and Chemotherapy 02/2014; 58(2). · 4.57 Impact Factor
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    ABSTRACT: The nature of the antigens recognized by γδ T cells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for Vδ1 TCR-expressing γδ T cells, the major γδ lymphocyte population in epithelial tissues. We crystallized a Vδ1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline Vδ1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3δ residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut Vδ1+ γδ T cells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by γδ T cells and reveal the prevalence of lipid recognition by innate-like T cell populations.
    Immunity 11/2013; · 19.80 Impact Factor
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    ABSTRACT: Increased serum levels of IL-15 are reported in type 1 diabetes (T1D). Here we report elevated serum soluble IL-15Rα levels in human T1D. To investigate the role of IL-15/IL-15Rα in the pathogenesis of T1D, we generated double transgenic mice with pancreatic β-cell expression of IL-15 and IL-15Rα. The mice developed hyperglycemia, marked mononuclear cell infiltration, β-cell destruction, and anti-insulin autoantibodies that mimic early human T1D. The diabetes in this model was reversed by inhibiting IL-15 signaling with anti-IL2/IL15Rβ (anti-CD122), which blocks IL-15 transpresentation. Furthermore, the diabetes could be reversed by administration of the Janus kinase 2/3 inhibitor tofacitinib, which blocks IL-15 signaling. In an alternative diabetes model, nonobese diabetic mice, IL15/IL-15Rα expression was increased in islet cells in the prediabetic stage, and inhibition of IL-15 signaling with anti-CD122 at the prediabetic stage delayed diabetes development. In support of the view that these observations reflect the conditions in humans, we demonstrated pancreatic islet expression of both IL-15 and IL-15Rα in human T1D. Taken together our data suggest that disordered IL-15 and IL-15Rα may be involved in T1D pathogenesis and the IL-15/IL15Rα system and its signaling pathway may be rational therapeutic targets for early T1D.
    Proceedings of the National Academy of Sciences 07/2013; · 9.74 Impact Factor
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    ABSTRACT: A major challenge of cancer immunotherapy is the persistence and outgrowth of subpopulations that lose expression of the target antigen. IL-15 is a potent cytokine that can promote organ-specific autoimmunity when up-regulated on tissue cells. Here we report that T cells eradicated 2-wk-old solid tumors that expressed IL-15, eliminating antigen-negative cells. In contrast, control tumors that lacked IL-15 expression consistently relapsed. Interestingly, even tumors lacking expression of cognate antigen were rejected when expressing IL-15, indicating that rejection after adoptive T-cell transfer was independent of cognate antigen expression. Nevertheless, the T-cell receptor of the transferred T cells influenced the outcome, consistent with the notion that T-cell receptor activation and effector status determine whether IL-15 can confer lymphokine killer activity-like properties to T cells. The effect was limited to the microenvironment of tumors expressing IL-15; there were no noticeable effects on contralateral tumors lacking IL-15. Taken together, these results indicate that expression of IL-15 in the tumor microenvironment may prevent the escape of antigen loss variants and subsequent tumor recurrence by enabling T cells to eliminate cancer cells lacking cognate antigen expression in a locally restricted manner.
    Proceedings of the National Academy of Sciences 05/2013; · 9.74 Impact Factor
  • Ludvig M Sollid, Bana Jabri
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    ABSTRACT: Coeliac disease, an inflammatory disease of the small intestine, shares key features with autoimmune disorders, such as susceptibility genes, presence of autoantibodies and T cell-mediated destruction of specific cells. Strikingly, however, continuous exposure to the exogenous dietary antigen gluten and gluten-specific adaptive immunity are required to maintain immunopathology. These observations challenge the notion that autoimmunity requires adaptive immune activation towards self antigens. Using coeliac disease as an example, we propose that other exogenous factors might be identified as drivers of autoimmune processes, in particular when evidence for T cells with specificity for self antigens driving the disease is lacking.
    Nature Reviews Immunology 03/2013; · 32.25 Impact Factor
  • Robert P Anderson, Bana Jabri
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    ABSTRACT: Recent interest in testing whether the success of antigen-specific immunotherapy (ASIT) for autoimmune diseases in mice can be translated to humans has highlighted the need for better tools to study and understand human autoimmunity. Clinical development of ASIT for allergy has been instructive, but limited understanding of CD4 T cell epitope/determinant hierarchies hampers the rational design and monitoring of ASIT. Definitive identification of pathogenic T cell epitopes as is now known in celiac disease and recent initiatives to optimize immune monitoring will facilitate rational design, monitoring and mechanistic understanding of ASIT for human autoimmune diseases.
    Current opinion in immunology 03/2013; · 10.88 Impact Factor
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    ABSTRACT: NK cells are large granular lymphocytes that form a critical component of the innate immune system, whose functions include the killing of cells expressing stress-induced molecules. It is increasingly accepted that despite being considered prototypical effector cells, NK cells require signals to reach their full cytotoxic potential. We previously showed that IL-15 is capable of arming CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2-dependent process. As NK cells also express NKG2D, we wanted to investigate whether this pathway functioned in an analogous manner and if resting NK cells could be primed to the effector phase by IL-15. Furthermore, to establish relevance to human disease we studied a possible role for this pathway in the pathogenesis of psoriatic arthritis, since there are aspects of this disease that suggest a potential effector role for the innate immune system. We found that PsA patients had upregulated IL-15 and MIC in their affected synovial tissues, and that this unique inflammatory environment enabled NK cell activation and killing via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint NK cells from blood NK cells by incubating them with IL-15. Altogether, these findings suggest a destructive role for NK cells when activated by environmental stress signals during the pathogenesis of PsA and demonstrate that IL-15 is capable of priming resting NK cells in tissues to the effector phase.
    PLoS ONE 01/2013; 8(9):e76292. · 3.73 Impact Factor
  • Sonia S Kupfer, Bana Jabri
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    ABSTRACT: Celiac disease results from the interplay of genetic, environmental, and immunologic factors. An understanding of the pathophysiology of celiac disease, in which the trigger (wheat, rye, and barley) is known, will undoubtedly reveal basic mechanisms that underlie other autoimmune diseases (eg, type 1 diabetes) that share many common pathogenic perturbations. This review describes seminal findings in each of the 3 domains of the pathogenesis of celiac disease, namely genetics, environmental triggers, and immune dysregulation, with a focus on newer areas of investigation such as non-HLA genetic variants, the intestinal microbiome, and the role of the innate immune system.
    Gastrointestinal endoscopy clinics of North America 10/2012; 22(4):639-60.
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    ABSTRACT: αβ T-cell lines specific for sulfatide, an abundant myelin glycosphingolipid presented by various CD1 molecules, have been previously derived from PBMCs of patients with demyelinating diseases such as multiple sclerosis (MS) but also from healthy subjects. Using an unbiased tetramer-based MACS enrichment method to enrich for rare antigen-specific cells, we confirmed the presence of CD1d-sulfatide-specific T cells in all healthy individuals examined. Surprisingly, the great majority of fresh sulfatide-specific T cells belonged to the γδ lineage. Furthermore, these cells used the Vδ1 TCR variable segment, which is uncommon in the blood but predominates in tissues such as the gut and specifically accumulates in MS lesions. Recombinant Vδ1 TCRs from different individuals were shown to bind recombinant CD1d-sulfatide complexes in a sulfatide-specific manner. These results provide the first direct demonstration of MHC-like-restricted, antigen-specific recognition by γδ TCRs. Together with previous reports, they support the notion that human Vδ1 T cells are enriched in CD1-specific T cells and suggest that the Vδ1 T-cell population that accumulates in MS lesions might be enriched in CD1-sulfatide-specific cells.
    European Journal of Immunology 07/2012; 42(9):2505-10. · 4.97 Impact Factor
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    ABSTRACT: The balance between regulatory and inflammatory immune responses is critical to maintain intestinal homeostasis. Furthermore, the nature of the inflammatory response needs to be tailored to the tissue to provide proper protective immunity while preserving host integrity. TLR2 (Toll-like receptor 2) is a unique TLR in that it has been shown to promote regulatory and inflammatory T cell responses. Using Yersinia enterocolitica, we show that oral infection promotes T(H)17 immunity, whereas systemic infection promotes T(H)1 immunity. Furthermore, induction of T(H)17 immunity during oral infection is dependent on TLR1 and results from the combinatorial effect of TLR2/TLR1-induced IL-6 and IL-23 and the presence of TGF-β in the intestinal environment. Interestingly, TLR2/TLR1 was not involved in T(H)1 immune responses during systemic infection, whereas the TLR2/TLR6 receptor complex induced IL-10(+) regulatory T cell responses during both systemic and oral infections. Our results reveal that the route of infection is central in determining which pathways provide protective immunity. Furthermore, they also demonstrate that TLR2 has dual immune functions in the gut and identify TLR1 as a critical innate receptor for protective intestinal T(H)17 immunity.
    Journal of Experimental Medicine 07/2012; 209(8):1437-44. · 13.21 Impact Factor
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    ABSTRACT: The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(−/−), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(−/−) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.
    Nature 06/2012; 487(7405):104-8. · 38.60 Impact Factor
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    ABSTRACT: Celiac disease is a T cell-mediated immune disorder induced by dietary gluten that is characterized by the development of an inflammatory anti-gluten CD4 T cell response, anti-gluten antibodies, and autoantibodies against tissue transglutaminase 2 and the activation of intraepithelial lymphocytes (IELs) leading to the destruction of the intestinal epithelium. Intraepithelial lymphocytes represent a heterogeneous population of T cells composed mainly of cytotoxic CD8 T cells residing within the epithelial layer, whose main role is to maintain the integrity of the epithelium by eliminating infected cells and promoting epithelial repair. Dysregulated activation of IELs is a hallmark of CD and is critically involved in epithelial cell destruction and the subsequent development of villous atrophy. In this review, we compare and contrast the phenotype and function of human and mouse small intestinal IELs under physiological conditions. Furthermore, we discuss how conditions of epithelial distress associated with overexpression of IL-15 and non-classical MHC class I molecules induce cytotoxic IELs to become licensed killer cells that upregulate activating NKG2D and CD94/NKG2C natural killer receptors, acquiring lymphokine killer activity. Pathways leading to dysregulated IEL activation could eventually be targeted to prevent villous atrophy and treat patients who respond poorly to gluten-free diet.
    Seminars in Immunopathology 06/2012; 34(4):551-66. · 5.38 Impact Factor
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    ABSTRACT: Natural killer (NK) cells inhibit early stages of tumor formation, recurrence, and metastasis. Here, we show that NK cells can also eradicate large solid tumors. Eradication depended on the massive infiltration of proliferating NK cells due to interleukin 15 (IL-15) released and presented by the cancer cells in the tumor microenvironment. Infiltrating NK cells had the striking morphologic feature of being densely loaded with periodic acid-Schiff-positive, diastase-resistant granules, resembling uterine NK cells. Perforin-mediated killing by these densely granulated NK cells was essential for tumor eradication. Expression of the IL-15 receptor α on cancer cells was needed to efficiently induce granulated NK cells, and expression on host stromal cells was essential to prevent tumor relapse after near complete destruction. These results indicate that IL-15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors.
    Cancer Research 02/2012; 72(8):1964-74. · 8.65 Impact Factor
  • Bana Jabri, Luis B Barreiro
    Nature Immunology 11/2011; 12(11):1029-30. · 26.20 Impact Factor
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    Ludvig M Sollid, Bana Jabri
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    ABSTRACT: Posttranslational modification (PTM) of antigen is a way to break T-cell tolerance to self-antigens and promote autoimmunity. However, the precise mechanisms by which modifications would facilitate autoimmune T-cell responses and how they relate to particular autoimmune-associated MHC molecules remain elusive. Celiac disease is a T-cell mediated enteropathy with a strong HLA association where the immune response is directed mainly against deamidated cereal gluten peptides that have been modified by the enzyme transglutaminase 2. The disease is further characterized by autoantibodies to transglutaminase 2 that have extraordinary high disease specificity and sensitivity. There have been important advances in the knowledge of celiac disease pathogenesis, and these insights may be applicable to other autoimmune disorders where PTM plays a role. This insight gives clues for understanding the involvement of PTMs in other autoimmune diseases.
    Current opinion in immunology 09/2011; 23(6):732-8. · 10.88 Impact Factor
  • R Troncone, B Jabri
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    ABSTRACT: Coeliac disease (CD) is a systemic immune-mediated disorder elicited by gluten in genetically susceptible individuals. The common factor for all patients with CD is the presence of a variable combination of gluten-dependent clinical manifestations, specific autoantibodies (anti-tissue transglutaminase/anti-endomysium), HLA-DQ2 and/or DQ8 haplotypes and different degrees of enteropathy. Recently, gluten sensitivity has received much interest, although the limits and possible overlap between gluten sensitivity and CD remain poorly defined. At present, a number of morphological, functional and immunological disorders that are lacking one or more of the key CD criteria (enteropathy, associated HLA haplotypes and presence of anti-transglutaminase two antibodies) but respond to gluten exclusion are included under the umbrella of gluten sensitivity. The possible immunological mechanisms underlying these conditions are discussed. Emphasis is given to specific autoantibodies as markers of the coeliac spectrum and to the hypothesis that innate epithelial stress can exist independently from adaptive intestinal immunity in gluten sensitivity.
    Journal of Internal Medicine 06/2011; 269(6):582-90. · 6.46 Impact Factor

Publication Stats

4k Citations
839.37 Total Impact Points

Institutions

  • 2006–2014
    • University of Illinois at Chicago
      • Department of Medicine (Chicago)
      Chicago, Illinois, United States
  • 2006–2013
    • University of Oslo
      • Department of Immunology (IMM)
      Oslo, Oslo, Norway
  • 2003–2013
    • University of Chicago
      • • Department of Pathology
      • • Department of Medicine
      • • Department of Microbiology
      Chicago, Illinois, United States
  • 2012
    • Université de Montréal
      • Department of Microbiology and Immunology
      Montréal, Quebec, Canada
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
    • University of Southern California
      • Department of Molecular Microbiology and Immunology
      Los Angeles, CA, United States
  • 2011
    • University of Naples Federico II
      • Department of Translational Medical Sciences
      Napoli, Campania, Italy
  • 2008
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
  • 2002–2006
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
  • 1999–2002
    • Princeton University
      • Department of Molecular Biology
      Princeton, NJ, United States
  • 2001
    • Rutgers New Jersey Medical School
      • Department of Medicine (RWJ Medical School)
      Newark, NJ, United States