title: Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.
abstract: Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15.
  
  
  
  We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice.
  
  
  
  Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood.
  
  
  
  α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion.
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zundler
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Raja
authors.initials: R
authors.lastname: Atreya
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Rath
authors.affiliation: Department of Dermatology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Voskens
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Hirschmann
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Rocío
authors.initials: R
authors.lastname: López-Posadas
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Watson
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker
authors.affiliation: Department of Dermatology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Neufert
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Atreya
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000097:blood / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000473:pathology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D011956:Receptors, Cell Surface / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; C523001:Gpr15 protein, mouse; D016023:Integrins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; C543529:vedolizumab
keywords: CYTOKINES; IMMUNOLOGY; INFLAMMATORY BOWEL DISEASE