{
  "abstract": "Background The peptide GPR15L is produced by colonic epithelial cells and has been implicated in T cell recruitment to the large intestine. However, its role in chronic colitis has been unclear so far.Objective To explore the role of GPR15L in the pathogenesis of experimental colitis and IBD.Design We studied how genetic deletion or overexpression of Gpr15l as well as rectal application of recombinant GPR15L alters the course of acute dextran sodium sulfate colitis and T cell transfer colitis. The impact of GPR15L on microbiota was explored with co-housing, littermate and faecal microbiota transfer studies, by 16S rRNA sequencing as well as anti-microbial assays and shotgun metagenomics. The expression of GPR15L was evaluated across three independent cohorts of patients with IBD and correlated to microbial diversity and flare-free survival.Results GPR15L clearly mitigated experimental colitis, but this was independent of T cell recruitment and GPR15. Instead, we observed that the effects of GPR15L were mediated by altered microbiomes in the large intestine and, consistently, showed that GPR15L acts as an antimicrobial peptide under anaerobic conditions and shapes microbial communities towards a homeostatic phenotype. Rectal supplementation of GPR15L counteracted experimental colitis. In patients with IBD, GPR15L expression was decreased in active inflammation, correlated with microbial diversity and was associated with flare-free survival.Conclusions GPR15L is a host-defence peptide that plays a beneficial role in the pathogenesis of intestinal inflammation. It seems promising to further evaluate its potential as a future therapeutic approach in IBD.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Miriana Leggio"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Sebastian Schramm"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Lisa Dietz"
    },
    {
      "affiliations": [
        "Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine and Palo Alto Veterans Medical Center, Stanford, Palo Alto, California, USA"
      ],
      "name": "Borja Ocón"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Stefan Wirtz"
    },
    {
      "affiliations": [
        "Department of Molecular Biology, Umeå University, Umeå, Sweden",
        "Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden"
      ],
      "name": "Fabiola Puertolas Balint"
    },
    {
      "affiliations": [
        "Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland"
      ],
      "name": "Bahtiyar Yilmaz"
    },
    {
      "affiliations": [
        "Institute of Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Jana Petzold"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Li-Juan Liu"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Mark Dedden"
    },
    {
      "affiliations": [
        "Institute of Human Genetics, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Arif Ekici"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany",
        "Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine and Palo Alto Veterans Medical Center, Stanford, Palo Alto, California, USA",
        "Department of Molecular Biology, Umeå University, Umeå, Sweden",
        "Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden",
        "Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland",
        "Institute of Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Institute of Human Genetics, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "TRR241 IBDome Consortium"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Xi Meng"
    },
    {
      "affiliations": [
        "Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "David Bingham"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Karen Anne-Marie Ullrich"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Stefanie Heltmann-Meyer"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Claudia Günther"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Kai Hildner"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Raja Atreya"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Imke Atreya"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Tanja M Müller"
    },
    {
      "affiliations": [
        "Institute of Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Roman G Gerlach"
    },
    {
      "affiliations": [
        "Department of Molecular Biology, Umeå University, Umeå, Sweden",
        "Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden"
      ],
      "name": "Bjoern O Schroeder"
    },
    {
      "affiliations": [
        "Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland"
      ],
      "name": "Andrew Macpherson"
    },
    {
      "affiliations": [
        "Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine and Palo Alto Veterans Medical Center, Stanford, Palo Alto, California, USA"
      ],
      "name": "Eugene C Butcher"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Markus F Neurath"
    },
    {
      "affiliations": [
        "Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Sebastian Zundler"
    }
  ],
  "title": "The endogenous peptide GPR15L shapes the intestinal microbiota to counteract colitis",
  "uid": "2bbd40e4-92ff-5210-8a9c-5e0ca90e1e86"
}