European Journal of Immunology

Cover image for Vol. 47 Issue 9

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Francesco Annunziato (Chairman of the Executive Committee)

Impact Factor: 4.227

ISI Journal Citation Reports © Ranking: 2016: 40/150 (Immunology)

Online ISSN: 1521-4141

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  1. 1 - 29
  1. Tissue immunology and leukocyte trafficking

    1. Research Articles

      Basic
      Interleukin-36 receptor mediates the crosstalk between plasma cells and synovial fibroblasts

      Verena Schmitt, Madelaine Hahn, Verena Kästele, Olga Wagner, Maximilian Wiendl, Anja Derer, Adriano Taddeo, Stefanie Hahne, Andreas Radbruch, Hans-Martin Jäck, Wolfgang Schuh, Dirk Mielenz, Steffen Gay, Georg Schett, Axel J Hueber and Silke Frey

      Version of Record online: 22 SEP 2017 | DOI: 10.1002/eji.201646788

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      Abstract

      In coculture, IL-36 receptor (IL-36R)-deficient synovial fibroblasts have reduced capacity to support survival of plasma cells compared to cells harboring IL-36R. We therefore suggest an IL-36R-dependent crosstalk between plasma cells and synovial fibroblasts providing a proinflammatory B cell/plasma cell niche in arthritic joints.

  2. Highlights

    1. Review

      Clinical
      You have free access to this content
      Adipose-tissue regulatory T cells: Critical players in adipose-immune crosstalk

      Maike Becker, Megan K. Levings and Carolin Daniel

      Version of Record online: 20 SEP 2017 | DOI: 10.1002/eji.201646739

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      Abstract

      A cross-talk between CD4+T cells and FoxP3+Tregs with adipose tissue shapes the local inflammatory environment in obesity-associated metabolic diseases. We discuss opportunities how the immunoregulatory properties of FoxP3+Tregs could be harnessed in order to maintain tissue-homeostasis in obesity and emphasize the need for more translational research on humans.

  3. Immunity to infection

    1. Research Articles

      Basic
      Immunological tolerance to LCMV antigens differently affects control of acute and chronic virus infection in mice

      Christina Woopen, Tobias Straub, Oliver Schweier, Ulrike Aichele, Katharina Düker, Thomas Boehm and Hanspeter Pircher

      Version of Record online: 15 SEP 2017 | DOI: 10.1002/eji.201747156

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      Abstract

      The role of LCMV glycoprotein (GP) versus nucleoprotein (NP) -derived epitopes for viral clearance was examined in LCMV antigen transgenic mice. Immunological tolerance to GP but not to NP abolished control of acute LCMV infection. In contrast, virus elimination was delayed to a similar extent in GP- and NP-transgenic mice after chronic LCMV infection.

  4. Transplantation and tolerance

    1. Short Communication

      Basic
      A20 deletion in T cells modulates acute graft-versus-host disease in mice

      Julius C. Fischer, Vera Otten, Katja Steiger, Martina Schmickl, Julia Slotta-Huspenina, Rudi Beyaert, Geert van Loo, Christian Peschel, Hendrik Poeck, Tobias Haas and Silvia Spoerl

      Version of Record online: 15 SEP 2017 | DOI: 10.1002/eji.201646911

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      Abstract

      After allogeneic hematopoietic stem cell transplantation in mice, A20−/− T cells display increased IFNγ production and higher rates of cell death compared to wild-type T cells. Depending on the T-cell dose, A20−/− T cells can thus induce more GVHD early but less GVHD late after transplantation.

  5. Immunomodulation and immune therapies

    1. Research Articles

      Basic
      You have full text access to this OnlineOpen article
      Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells

      Maria Pasztoi, Joern Pezoldt, Michael Beckstette, Christoph Lipps, Dagmar Wirth, Manfred Rohde, Krisztina Paloczi, Edit Iren Buzas and Jochen Huehn

      Version of Record online: 15 SEP 2017 | DOI: 10.1002/eji.201746960

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      The Treg-inducing capacity of immortalized fibroblastic reticular cells isolated from the gut-draining mesenteric lymph nodes was assessed by in vitro assays and RNA-seq analysis. Here we provide evidence for the release of TGF-β-carrying microvesicles by stromal cells fostering Treg induction and offer a new mechanism of intestinal tolerance.

    2. Minimally manipulated murine regulatory T cells purified by reversible Fab Multimers are potent suppressors for adoptive T-cell therapy

      Fabian Mohr, Julius Clemens Fischer, Marc Nikolaus, Christian Stemberger, Stefan Dreher, Admar Verschoor, Tobias Haas, Hendrik Poeck and Dirk H. Busch

      Version of Record online: 15 SEP 2017 | DOI: 10.1002/eji.201747137

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      We developed a one-step positive enrichment protocol for highly pure regulatory T cell that allowed subsequent release of the isolation reagent from the cell surface using Fab multimers. This removal of isolation reagents led to better engraftment of Treg cells and to better in vivo protection from experimental acute GvHD.

    3. AhR activation increases IL-2 production by alloreactive CD4+ T cells initiating the differentiation of mucosal-homing Tim3+Lag3+ Tr1 cells

      Allison K. Ehrlich, Jamie M. Pennington, Susan Tilton, Xisheng Wang, Nikki B. Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K. Kolluri and Nancy I. Kerkvliet

      Version of Record online: 15 SEP 2017 | DOI: 10.1002/eji.201747121

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      AhR activation in alloantigen-stimulated CD4+ T cells leads to increased IL-2 production. Excess IL-2 drives increased expression of CD25, CTLA4 and GITR, initiating AhR-Tr1 cell differentiation. AhR-Tr1 cells coexpress Lag3, Tim3, and either CCR4 or CCR9, and suppress effector T cell proliferation. AhR-Tr1 cells subsequently accumulate in mucosal tissues.

  6. Immunity to infection

    1. Research Articles

      Clinical
      CTLA-4-expression on VZV-specific T cells in CSF and blood is specifically increased in patients with VZV related central nervous system infections

      David Schub, Mathias Fousse, Klaus Faßbender, Barbara C. Gärtner, Urban Sester, Martina Sester and Tina Schmidt

      Version of Record online: 14 SEP 2017 | DOI: 10.1002/eji.201747079

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      Identification of the causative pathogen of CNS-infections is challenging. Analysis of VZV-specific CD4+ T cells from CSF and blood of patients with active CNS-diseases showed that VZV-related CNS-infections are associated with enrichment of VZV-specific T cells in the CSF, and increased expression of CTLA-4 on VZV-specific T cells from both CSF and blood.

  7. Immunomodulation and immune therapies

    1. Research Articles

      Basic
      You have full text access to this OnlineOpen article
      Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways

      Cristina Cirauqui, Cristina Benito-Villalvilla, Silvia Sánchez-Ramón, Sofía Sirvent, Carmen M. Diez-Rivero, Laura Conejero, Paola Brandi, Lourdes Hernández-Cillero, Juliana Lucía Ochoa, Beatriz Pérez-Villamil, David Sancho, José Luis Subiza and Oscar Palomares

      Version of Record online: 14 SEP 2017 | DOI: 10.1002/eji.201747024

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      MV130, a polybacterial preparation to treat recurrent respiratory infections, promotes the generation of Th1, Th17 and IL-10 immune responses against related and unrelated antigens via RIPK2 and MyD88-mediated signalling pathways. These findings might well pave the way for alternative treatments in other clinical conditions with high risk of recurrent infections.

  8. Adaptive immunity

    1. Research Articles

      Basic
      Ablation of the Cβ2 subunit of PKA in immune cells leads to increased susceptibility to systemic inflammation in mice

      Line Victoria Moen, Zeynep Sener, Roman Volchenkov, Anja Camilla Svarstad, Aud Marit Eriksen, Halvor L. Holen and Bjørn S. Skålhegg

      Version of Record online: 14 SEP 2017 | DOI: 10.1002/eji.201646809

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      Lymphocytes express three different forms of the catalytic subunit of PKA called Calpha1, Cbeta1 and Cbeta2. Whereas Calpha1 regulates lymphocyte proliferation the role of Cbeta in lymphocytes is enigmatic. We show that mice lacking Cbeta2 are hypersensitive to inflammation suggesting that Cbeta2 regulates immune sensitivity to foreign substances.

  9. Immunity to infection

    1. Research Articles

      Clinical
      Patterns of protective associations differ for antibodies to P.falciparum-infected erythrocytes and merozoites in immunity against malaria in children

      Jo-Anne Chan, Danielle I Stanisic, Michael F Duffy, Leanne J Robinson, Enmoore Lin, James W Kazura, Christopher L King, Peter M Siba, Freya JI Fowkes, Ivo Mueller and James G Beeson

      Version of Record online: 13 SEP 2017 | DOI: 10.1002/eji.201747032

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      Antibodies to surface antigens of P. falciparum-infected erythrocytes were associated with protection against symptomatic malaria in younger and older children, while antibodies to merozoite antigens were only protective in older children.

      PfEMP1 is the major target of antibodies to the surface of infected erythrocytes among children from Papua New Guinea

  10. Highlights

    1. Mini-Review

      Clinical
      Wiskott-Aldrich syndrome protein: Emerging mechanisms in immunity

      Elizabeth Rivers and Adrian J. Thrasher

      Version of Record online: 12 SEP 2017 | DOI: 10.1002/eji.201646715

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      WASP is an important regulator of the actin cytoskeleton with roles in immune cell functions such as cell migration, immune synapse assembly, phagocytosis and cytokine release. Cytoskeleton-independent roles in nuclear transcription are also described. Review of WASP research in human and murine models provides valuable insight into WAS disease pathology.

      F-actin, filamentous actin; WAS, Wiskott Aldrich syndrome; WASP, Wiskott Aldrich syndrome protein

  11. Molecular immunology and signaling

    1. Research Articles

      Basic
      You have full text access to this OnlineOpen article
      TCR signalling network organization at the immunological synapses of murine regulatory T cells

      Marco van Ham, René Teich, Lars Philipsen, Jana Niemz, Nicole Amsberg, Josef Wissing, Manfred Nimtz, Lothar Gröbe, Stefanie Kliche, Nadine Thiel, Frank Klawonn, Mario Hubo, Helmut Jonuleit, Peter Reichardt, Andreas J. Müller, Jochen Huehn and Lothar Jänsch

      Version of Record online: 12 SEP 2017 | DOI: 10.1002/eji.201747041

      Thumbnail image of graphical abstract

      Using proteomics, phosphoproteomics and MELC analyses we comparatively analysed the molecular inventory, TCR responses and dynamic distribution of TCR signalling components in Treg cells and Tconv cells. Treg cells show a pre-activated phenotype, a unique activation response of cytoskeleton-associated proteins and a unique immunological synapse assembly.

  12. Immunodeficiencies and autoimmunity

    1. Research Articles

      Clinical
      You have full text access to this OnlineOpen article
      Human neonatal thymectomy induces altered B-cell responses and autoreactivity

      Theo van den Broek, Asaf Madi, Eveline M. Delemarre, Alvin W. L. Schadenberg, Kiki Tesselaar, José A. M. Borghans, Stefan Nierkens, Frank A. Redegeld, Henny G. Otten, Maura Rossetti, Salvatore Albani, Rachel Sorek, Irun R. Cohen, Nicolaas J. G. Jansen and Femke van Wijk

      Version of Record online: 6 SEP 2017 | DOI: 10.1002/eji.201746971

      Thumbnail image of graphical abstract

      Neonatal Tx results in T-cell lymphopenia with subsequent homeostatic T-cell proliferation and memory T-cell expansion, but an unaltered B-cell phenotype. The antibody repertoire is skewed toward autoreactivity following memory T-cell expansion. Preferential expansion of regulatory T cells might prevent autoreactivity from developing into autoimmune disease.

  13. Immunomodulation and immune therapies

    1. Research Articles

      Basic
      You have full text access to this OnlineOpen article
      Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration

      Marieke H. Heineke, Lydia P.E. van der Steen, Rianne M. Korthouwer, J. Joris Hage, Johannes P.M. Langedijk, Joris J. Benschop, Jantine E. Bakema, Jerry W. Slootstra and Marjolein van Egmond

      Version of Record online: 6 SEP 2017 | DOI: 10.1002/eji.201646782

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      The interaction between IgA and the IgA Fc receptor (FcαRI) leads to potent neutrophil activation and migration, resulting in tissue damage in IgA-mediated autoimmune skin blistering diseases. Here we show the therapeutic potential of peptide mimetics that block the interaction between IgA and FcαRI.

  14. Allergy and inflammation

    1. Research Articles

      Basic
      Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions via MRGPRX2 and its murine homologue MRGPRB2

      Tao Zhang, Delu Che, Rui Liu, Shengli Han, Nan Wang, Yingzhuan Zhan, Priyanka Pundir, Jiao Cao, Yanni Lv, Liu Yang, Jue Wang, Meiwen Ding, Xinzhong Dong and Langchong He

      Version of Record online: 4 SEP 2017 | DOI: 10.1002/eji.201746951

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      MRGPRX2/B2 mediated drug anaphylactoid reaction of five types of antimicrobials were screened and analysed in vivo and in vitro. We implicate that agents containing nitrogen atom easily protonated is the key characteristics for activation of the receptors. These results provide insight into antimicrobial induced anaphylactoid reactions.

  15. Immunity to infection

    1. Research Articles

      Basic
      Herpes simplex virus 1 interferes with autophagy of murine dendritic cells and impairs their ability to stimulate CD8+ T lymphocytes

      Ramachandramouli Budida, Metodi V. Stankov, Katinka Döhner, Anna Buch, Diana Panayotova-Dimitrova, Kim A. Tappe, Anja Pohlmann, Beate Sodeik and Georg M. N. Behrens

      Version of Record online: 31 AUG 2017 | DOI: 10.1002/eji.201646908

      Thumbnail image of graphical abstract

      ICP34.5 protein of HSV-1 helps the virus to counteract host cell responses such as translational shutoff and autophagic degradation (left). Deletion of ICP34.5 restores efficient MHC class I presentation via autophagy despite reduced abundance of viral antigens (right).

  16. Highlights

    1. Mini-Review

      Basic
      Contributions of the intestinal microbiome in lung immunity

      Jeremy P. McAleer and Jay K. Kolls

      Version of Record online: 31 AUG 2017 | DOI: 10.1002/eji.201646721

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      Interactions between the intestinal microbiota, environment and immune system contribute to the development of asthma and atopy. We discuss epidemiologic, clinical and mechanistic data on the role of microbes in regulating lung immunity. Dietary manipulation of microbiota is further discussed as potential adjunctive therapies for chronic inflammatory diseases.

  17. Molecular immunology and signaling

    1. Research Articles

      Basic
      Absence of Notch1 in murine myeloid cells attenuates the development of experimental autoimmune encephalomyelitis by affecting Th1 and Th17 priming

      Miriam Fernández, Eva M. Monsalve, Susana López-López, Almudena Ruiz-García, Susana Mellado, Elena Caminos, José Javier García-Ramírez, Jorge Laborda, Pedro Tranque and María José M. Díaz-Guerra

      Version of Record online: 31 AUG 2017 | DOI: 10.1002/eji.201646901

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      We demonstrate that the absence of the NOCTH1 receptor in myeloid cells limits the priming of Th1 and Th17 cells, attenuating the development of murine Experimental Autoimmune Encephalomyelitis

    2. Glucocorticoids downregulate TLR4 signaling activity via its direct targeting by miR-511-5p

      Graziella Curtale, Tiziana A. Renzi, Lorenzo Drufuca, Marcello Rubino and Massimo Locati

      Version of Record online: 31 AUG 2017 | DOI: 10.1002/eji.201747044

      Thumbnail image of graphical abstract

      LPS and other inflammatory stimuli repress miR-511-5p expression in human monocytes, while anti-inflammatory stimuli, such as TGF-β and glucocorticoids, have the opposite effect. Downregulation of TLR4 by miR-511-5 is responsible for glucocorticoids- and TGF-β-mediated inhibition of pro-inflammatory cytokines production observed in endotoxin tolerant monocytes.

  18. Adaptive immunity

    1. Research Articles

      Basic
      IgG subclass and vaccination stimulus determine changes in antigen specific antibody glycosylation in mice

      Daniela Kao, Anja Lux, Anja Schaffert, Roland Lang, Friedrich Altmann and Falk Nimmerjahn

      Version of Record online: 29 AUG 2017 | DOI: 10.1002/eji.201747208

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      Depending on the type of activation and costimulation, B cells develop into plasma blasts and plasma cells and produce IgG antibodies of different subclasses. These individual IgG subclasses have a distinct glycosylation profile, suggesting that IgG class switching and glycosylation are linked.

  19. Immunity to infection

    1. Research Articles

      Clinical
      High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence

      Abderaouf Damouche, Guillaume Pourcher, Valérie Pourcher, Stéphane Benoist, Elodie Busson, Jean-Jacques Lataillade, Mélanie Le Van, Thierry Lazure, Julien Adam, Benoit Favier, Bruno Vaslin, Michaela Müller-Trutwin, Olivier Lambotte and Christine Bourgeois

      Version of Record online: 28 AUG 2017 | DOI: 10.1002/eji.201747060

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      Adipose tissue CD4 T cells exhibit a tissue-specific profile defined by high expression of PD-1. The functional relevance of such high PD-1 expression on adipose CD4 T cells remains unclear but it may favor HIV persistence since PD1 expressing CD4 T cells has been described as a preferential HIV reservoir.

  20. Adaptive immunity

    1. Research Articles

      Basic
      Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice

      Alison Hogg, Yongjun Sui, Shlomo Z. Ben-Sasson, William E. Paul and Jay A. Berzofsky

      Version of Record online: 28 AUG 2017 | DOI: 10.1002/eji.201747091

      Thumbnail image of graphical abstract

      CD4 subset Th1 cells help Tc1 cells that make IFN-γ, controlling virus infection. Th17 cells instead promote immune-deviation to Tc17 cells, making IL-17 and not controlling virus, thus providing inadequate help. IL-1β with TGF-β induce Th17 cells, so TGF-β blockade inhibits this immune deviation without blocking adjuvant effects of IL-1β.

    2. T cell-dependent antigen adjuvanted with DOTAP-CpG-B but not DOTAP-CpG-A induces robust germinal center responses and high affinity antibodies in mice

      Munir Akkaya, Billur Akkaya, Patrick W. Sheehan, Pietro Miozzo, Mirna Pena, Chen-Feng Qi, Javier Manzella-Lapeira, Silvia Bolland and Susan K. Pierce

      Version of Record online: 21 AUG 2017 | DOI: 10.1002/eji.201747113

      Thumbnail image of graphical abstract

      Conjugation of CpG containing synthetic ODNs with DOTAP leads to an increase in their immune-adjuvant potential in a ODN type dependent fashion. Mice immunized with a T cell dependent antigen (NP-CGG) adjuvanted with unconjugated CpG-A or CpG-B fail to generate strong immune response. On the other hand immunization of mice with NP-CGG adjuvanted with DOTAP conjugated CpG-B but not CpG-A lead to a strong antigen specific immune response.

  21. Immunodeficiencies and autoimmunity

    1. Research Articles

      Clinical
      Reduced numbers of circulating group 2 innate lymphoid cells in patients with common variable immunodeficiency

      Christoph B. Geier, Sophie Kraupp, David Bra, Martha M. Eibl, Jocelyn R. Farmer, Krisztian Csomos, Jolan E. Walter and Hermann M. Wolf

      Version of Record online: 14 AUG 2017 | DOI: 10.1002/eji.201746961

      Thumbnail image of graphical abstract

      Innate lymphoid cells type 2 are reduced in patients with common variable immunodeficiency. ILC2 deficiency correlates with B-cell abnormalities and chronic enteropathy. CVID ILC2 do not express MCHII and CD25 upon activation.2

  22. Molecular immunology and signaling

    1. Short Communication

      Basic
      The inflammatory cytokine interferon-gamma inhibits sortilin-1 expression in hepatocytes via the JAK/STAT pathway

      John Pirault, Konstantinos A. Polyzos, Marcelo H. Petri, Daniel F. J. Ketelhuth, Magnus Bäck and Göran K. Hansson

      Version of Record online: 14 AUG 2017 | DOI: 10.1002/eji.201646768

      Thumbnail image of graphical abstract

      We demonstrated by cultures, chromatin immunoprecipitation assays and disruption of the JAK/STAT1 signaling pathway that the treatment of hepatocytes with the inflammatory cytokine IFN-γ induced the repression of sortilin-1.

  23. Immunity to infection

    1. Research Articles

      Basic
      Dual role of monocyte-derived dendritic cells in Trypanosoma cruzi infection

      Carolina V. Poncini and Stella M. González-Cappa

      Version of Record online: 14 AUG 2017 | DOI: 10.1002/eji.201646830

      Thumbnail image of graphical abstract

      During Trypanosoma cruzi infection anti-parasite response is delayed in time. After skin-infection, there is a failure in leukocyte mobilization to the parasite site of entry, followed by monocyte recruitment to secondary lymphoid organs. Monocyte-derived cells result critical in control the parasite spreading and in sustaining its persistence into the host.

  24. Leukocyte and lymphoid organ ontogeny

    1. Research Articles

      Basic
      EBI2 contributes to the induction of thymic central tolerance in mice by promoting rapid motility of medullary thymocytes

      Sanghee Ki, Hiran M. Thyagarajan, Zicheng Hu, Jessica N. Lancaster and Lauren I.R. Ehrlich

      Version of Record online: 9 AUG 2017 | DOI: 10.1002/eji.201747020

      Thumbnail image of graphical abstract

      Developing T cells must enter the thymic medulla and scan numerous antigen presenting cells to encounter the full range of self-antigens required to induce central tolerance. EBI2, a chemokine receptor expressed by immature medullary thymocytes, promotes thymocyte medullary accumulation and rapid motility, thus contributing to the induction of central tolerance.

  25. Immunity to infection

    1. Research Articles

      Basic
      Persistent accumulation of gut macrophages with impaired phagocytic function correlates with SIV disease progression in macaques

      Zachary D. Swan, Anthea L. Bouwer, Elizabeth R. Wonderlich and Simon M. Barratt-Boyes

      Version of Record online: 24 JUL 2017 | DOI: 10.1002/eji.201646904

      Thumbnail image of graphical abstract

      Macaques with progressive SIV infection have damaged gut mucosa that contains a high number of macrophages. These macrophages are noninflammatory but poorly phagocytic and fail to adequately clear tissue debris. This impaired phagocytic function potentially leads to persistent macrophage recruitment to the mucosa.

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