Differential effects of ?4?7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

Fischer A, Zundler S, Atreya R, Rath T, Voskens C, Hirschmann S, Lopez Posadas R, Watson A, Becker C, Schuler G, Neufert C, Atreya I, Neurath M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Gut BMJ Publishing Group

Book Volume: 65

Pages Range: 1642-64

Journal Issue: 10

DOI: 10.1136/gutjnl-2015-310022

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 ?4?7 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 ?4?7 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 ?4?7 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.?4?7 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 with CRIS profile

Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Rocío Lopez Posadas Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie Gerold Schuler Lehrstuhl für Haut- und Geschlechtskrankheiten Clemens Neufert Medizinische Fakultät Markus Neurath Lehrstuhl für Innere Medizin I

Involved external institutions

University of East Anglia GB United Kingdom (GB)

How to cite

APA:

Fischer, A., Zundler, S., Atreya, R., Rath, T., Voskens, C., Hirschmann, S.,... Neurath, M. (2016). Differential effects of ?4?7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo. Gut, 65(10), 1642-64. https://doi.org/10.1136/gutjnl-2015-310022

MLA:

Fischer, Anika, et al. "Differential effects of ?4?7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo." Gut 65.10 (2016): 1642-64.

BibTeX: Download