Bana Jabri

University of Chicago, Chicago, Illinois, United States

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Publications (89)1180.42 Total impact

  • Bana Jabri · Valérie Abadie ·
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    ABSTRACT: In this Opinion article, we discuss the function of tissues as a crucial checkpoint for the regulation of effector T cell responses, and the notion that interleukin-15 (IL-15) functions as a danger molecule that communicates to the immune system that the tissue is under attack and poises it to mediate tissue destruction. More specifically, we propose that expression of IL-15 in tissues promotes T helper 1 cell-mediated immunity and provides co-stimulatory signals to effector cytotoxic T cells to exert their effector functions and drive tissue destruction. Therefore, we think that IL-15 contributes to tissue protection by promoting the elimination of infected cells but that when its expression is chronically dysregulated, it can promote the development of complex T cell-mediated disorders associated with tissue destruction, such as coeliac disease and type 1 diabetes.
    Nature Reviews Immunology 11/2015; DOI:10.1038/nri3919 · 34.99 Impact Factor
  • R. Bouziat · B. Jabri ·

    Science 11/2015; 350(6262):742-743. DOI:10.1126/science.aad6768 · 33.61 Impact Factor
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    ABSTRACT: T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or following fecal transfer. 16S ribosomal RNA sequencing identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as anti-PD-L1 therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.
    Science 11/2015; DOI:10.1126/science.aac4255 · 33.61 Impact Factor
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    ABSTRACT: Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota. We investigated whether specific microbiota compositions influence immune responses to gluten in mice expressing the human DQ8 gene, which confers moderate CD genetic susceptibility. Germ-free mice, clean specific-pathogen-free (SPF) mice colonized with a microbiota devoid of opportunistic pathogens and Proteobacteria, and conventional SPF mice that harbor a complex microbiota that includes opportunistic pathogens were used. Clean SPF mice had attenuated responses to gluten compared to germ-free and conventional SPF mice. Germ-free mice developed increased intraepithelial lymphocytes, markers of intraepithelial lymphocyte cytotoxicity, gliadin-specific antibodies, and a proinflammatory gliadin-specific T-cell response. Antibiotic treatment, leading to Proteobacteria expansion, further enhanced gluten-induced immunopathology in conventional SPF mice. Protection against gluten-induced immunopathology in clean SPF mice was reversed after supplementation with a member of the Proteobacteria phylum, an enteroadherent Escherichia coli isolated from a CD patient. The intestinal microbiota can both positively and negatively modulate gluten-induced immunopathology in mice. In subjects with moderate genetic susceptibility, intestinal microbiota changes may be a factor that increases CD risk.
    American Journal Of Pathology 10/2015; 185(11). DOI:10.1016/j.ajpath.2015.07.018 · 4.59 Impact Factor
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    ABSTRACT: Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor-independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell-mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated. © 2015 Tang et al.
    Journal of Experimental Medicine 08/2015; DOI:10.1084/jem.20150303 · 12.52 Impact Factor
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    ABSTRACT: Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 08/2015; 43(3). DOI:10.1016/j.immuni.2015.08.007 · 21.56 Impact Factor
  • Elena F Verdu · Heather J Galipeau · Bana Jabri ·
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    ABSTRACT: Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause-effect relationships and to identify agents for modulating the gut microbiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gut microbiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host-microbial interactions can influence host responses to gluten.
    Nature Reviews Gastroenterology &#38 Hepatology 06/2015; 12(9). DOI:10.1038/nrgastro.2015.90 · 12.61 Impact Factor
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    ABSTRACT: Background & aims: The mechanisms of tissue destruction during progression of celiac disease are poorly defined. It is not clear how tissue stress and adaptive immunity contribute to the activation of intraepithelial cytotoxic T cells and the development of villous atrophy. We analyzed epithelial cells and intraepithelial cytotoxic T cells in family members of patients with celiac disease, who were without any signs of adaptive antigluten immunity, and in potential celiac disease patients, who have antibodies against tissue transglutaminase 2 in the absence of villous atrophy. Methods: We collected blood and intestinal biopsy specimens from 268 patients at tertiary medical centers in the United States and Italy from 2004 to 2012. All subjects had normal small intestinal histology. Study groups included healthy individuals with no family history of celiac disease or antibodies against tissue transglutaminase 2 (controls), healthy family members of patients with celiac disease, and potential celiac disease patients. Intraepithelial cytotoxic T cells were isolated and levels of inhibitory and activating natural killer (NK) cells were measured by flow cytometry. Levels of heat shock protein (HSP) and interleukin 15 were measured by immunohistochemistry, and ultrastructural alterations in intestinal epithelial cells (IECs) were assessed by electron microscopy. Results: IECs from subjects with a family history of celiac disease, but not from subjects who already had immunity to gluten, expressed higher levels of HS27, HSP70, and interleukin-15 than controls; their IECs also had ultrastructural alterations. Intraepithelial cytotoxic T cells from relatives of patients with celiac disease expressed higher levels of activating NK receptors than cells from controls, although at lower levels than patients with active celiac disease, and without loss of inhibitory receptors for NK cells. Intraepithelial cytotoxic T cells from potential celiac disease patients failed to up-regulate activating NK receptors. Conclusions: A significant subset of healthy family members of patients with celiac disease with normal intestinal architecture had epithelial alterations, detectable by immunohistochemistry and electron microscopy. The adaptive immune response to gluten appears to act in synergy with epithelial stress to allow intraepithelial cytotoxic T cells to kill epithelial cells and induce villous atrophy in patients with active celiac disease.
    Gastroenterology 05/2015; 149(3). DOI:10.1053/j.gastro.2015.05.013 · 16.72 Impact Factor
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    Sangman Michael Kim · Toufic Mayassi · Bana Jabri ·
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    ABSTRACT: Celiac disease is a T cell mediated immune disorder characterized by the loss of oral tolerance to dietary gluten and the licensing of intraepithelial lymphocytes to kill intestinal epithelial cells, leading to villous atrophy. Innate immunity plays a critical role in both of these processes and cytokines such as interleukin-15 and interferon-α can modulate innate processes such as polarization of dendritic cells as well as intraepithelial lymphocyte function. These cytokines can be modulated by host microbiota, which can also influence dendritic cell function and intraepithelial lymphocyte homeostasis. We will elaborate on the role of interleukin-15, interferon-α, and the microbiota in modulating the processes that lead to loss of tolerance to gluten and tissue destruction in celiac disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology 05/2015; 29(3). DOI:10.1016/j.bpg.2015.05.001 · 3.48 Impact Factor
  • Valérie Abadie · Bana Jabri ·
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    ABSTRACT: Celiac disease (CD) is a T cell-mediated intestinal disorder induced by dietary gluten in genetically susceptible individuals. It is a prototypic example of how the interaction between predisposing genes (human leukocyte antigen (HLA) and non-HLA genes) and the environment (gluten) can lead to the development of complex inflammatory disorders. Although anti-gluten CD4+ T cells are central in all aspects of CD pathogenesis, from the loss of oral tolerance to the generation of antibodies, intraepithelial cytotoxic CD8+ T lymphocytes are indispensable to promote intestinal tissue destruction. Furthermore, posttranslational modifications mediated by tissue transglutaminase-2 appear to be key in the initiation and/or amplification of anti-gluten T cell immunity. Despite many advances in our understanding of CD pathophysiology, how distinct immunological pathways cooperate to promote the destruction of intestinal epithelial cells is not yet fully understood. Here we summarize our current knowledge on the immunobiology of CD and discuss future research perspectives.
  • Bana Jabri · Cox Terhorst ·

    Current Opinion in Immunology 11/2014; 31C:v-vii. DOI:10.1016/j.coi.2014.10.010 · 7.48 Impact Factor

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    ABSTRACT: The origin and developmental pathway of intestinal T cell receptor αβ(+) CD4(-)CD8β(-) intraepithelial lymphocytes (unconventional iIELs), a major population of innate-like resident cytolytic T cells, have remained elusive. By cloning and expressing several TCRs isolated from unconventional iIELs, we identified immature CD4(lo)CD8(lo)(DP(lo))CD69(hi)PD-1(hi) thymocytes as the earliest postsignaling precursors for these cells. Although these precursors displayed multiple signs of elevated TCR signaling, a sizeable fraction of them escaped deletion to selectively engage in unconventional iIEL differentiation. Conversely, TCRs cloned from DP(lo)CD69(hi)PD-1(hi) thymocytes, a population enriched in autoreactive thymocytes, selectively gave rise to unconventional iIELs upon transgenic expression. Thus, the unconventional iIEL precursor overlaps with the DP(lo) population undergoing negative selection, indicating that, concomitant with the downregulation of both CD4 and CD8 coreceptors, a balance between apoptosis and survival signals results in outcomes as divergent as clonal deletion and differentiation to the unconventional iIEL lineage.
    Immunity 08/2014; 41(2). DOI:10.1016/j.immuni.2014.07.008 · 21.56 Impact Factor
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    ABSTRACT: Background and aim: 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). Methods: We contacted all 28 pathology departments in Sweden, and through biopsy reports identified 26,739 individuals with CD. We then compared the prevalence of ever using oral isotretinoin to the prevalence in 134,277 matched controls through conditional logistic regression. Data on isotretinoin exposure were obtained from the national Swedish Prescribed Drug Registry. As the only indication for isotretinoin use in Sweden is acne, we also examined its relationship to CD. Data on acne were obtained from the Swedish Patient Registry. Results: Ninety-three individuals with CD (0.35 %) and 378 matched controls (0.28 %) had a prescription of isotretinoin. This corresponded to an odds ratio (OR) of 1.22 [95 % confidence interval (CI) 0.97-1.54]. Risk estimates were similar in men and women, and when we restricted our data to individuals diagnosed after the start of the Prescribed Drug Registry. Restricting our analyses to individuals diagnosed aged 12-45 years did not influence the risk estimates (OR 1.38, 95 % CI 0.97-1.97). Meanwhile, having a diagnosis of acne was positively associated with CD (OR 1.34, 95 % CI 1.20-1.51). Conclusions: This study found no association between isotretinoin use and CD, but a small excess risk of CD in patients with a diagnosis of acne.
    American Journal of Clinical Dermatology 07/2014; 15(6). DOI:10.1007/s40257-014-0090-8 · 2.73 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. DOI:10.1111/imr.12191 · 10.12 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.
    The Journal of Immunology 06/2014; 193(2). DOI:10.4049/jimmunol.1400556 · 4.92 Impact Factor
  • Bana Jabri · Xi Chen · Ludvig M Sollid ·

    Nature Structural & Molecular Biology 04/2014; 21(5). DOI:10.1038/nsmb.2826 · 13.31 Impact Factor

  • Journal of Surgical Research 02/2014; 186(2):591. DOI:10.1016/j.jss.2013.11.544 · 1.94 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 manyMDR 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 eliminateMDRpathogens by using an agent that interferes with the ability of colonizing pathogens to express virulence in response to hostderived 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. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 02/2014; 58(2). DOI:10.1128/AAC.02183-13 · 4.48 Impact Factor

Publication Stats

5k Citations
1,180.42 Total Impact Points


  • 2003-2015
    • University of Chicago
      • • Department of Pathology
      • • Committee on Immunology
      • • Department of Medicine
      Chicago, Illinois, United States
    • Columbia University
      New York, New York, United States
  • 2012
    • University of Padova
      Padua, Veneto, Italy
  • 2006-2011
    • University of Illinois at Chicago
      • Department of Pediatrics (Peoria)
      Chicago, Illinois, United States
  • 1999-2002
    • Princeton University
      • Department of Molecular Biology
      Princeton, New Jersey, United States
  • 2001
    • Mount Sinai Medical Center
      New York, New York, United States
  • 2000
    • Université René Descartes - Paris 5
      • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France
  • 1998
    • Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor)
      Créteil, Île-de-France, France