HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) All Versions of this Article: gut.2006.091181v1 56/1/52    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Santucci, L Articles by Riccardi, C Search for Related Content PubMed PubMed Citation Articles by Santucci, L Articles by Riccardi, C Topic Collections Related Article

GITR modulates innate and adaptive mucosal immunity during the development of experimental colitis in mice

¹ Clinica di Gastroenterologia ed Endoscopia Digestiva, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Perugia, Italy
² Istituto di Farmacologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Perugia, Italy

Correspondence to:
Correspondence to:
Dr L Santucci
Clinica di Gastroenterologia ed Epatologia, Dipartimento di Scienze Chirurgiche, Gastroenterologiche ed Epatologiche, Università di Perugia, Policlinico Monteluce, 06122 Perugia, Italy; lsant{at}unipg.it

Background: Uncontrolled T cell activation and abnormal function of the innate immune system against normal enteric bacterial flora play a critical part in the pathogenesis of inflammatory bowel disease (IBD). Therefore, pharmacological strategies directed to restore the normal responsiveness of the immune system could be efficacious in the treatment of these pathological conditions. Glucocorticoid-induced tumour necrosis factor receptor (GITR)-related gene is a member of the tumour necrosis factor receptor superfamily that is constitutively expressed at high levels on regulatory T cells and at low levels on unstimulated T cells, B cells and macrophages. GITR triggering leads to activation of T effectors and reversal of suppressive function of regulatory T cells.

Aim: To investigate the role of GITR in the development of experimental colitis in mice.

Results: Using GITR^–/– mice, GITR deletion protected against 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis by reducing innate immune responses and effector T cell activity. Effector T cells isolated from GITR^–/– mice were less effective than T cells isolated from GITR^+/+ mice to transfer colitis in immunodeficient mice. Blocking the GITR/ligand for GITR (GITRL) signal by giving soluble GITR prevented TNBS-induced colitis in normal GITR^+/+ and also in lymphocyte-deficient SCID mice.

Conclusions: Collectively, these data suggest that GITR plays a critical part in regulating both acquired and innate mucosal immune responses during the development of experimental colitis in mice. Therefore, targeting the GITR/GITRL system signalling may represent a potential pharmacological tool for the treatment of IBD.

Abbreviations: FITC, fluorescence isothiocyanate; GITR, glucocorticoid-induced tumour necrosis factor receptor; GITRL, ligand for GITR; IBD, inflammatory bowel disease; IFN, interferon; LPMC, lamina propria mononuclear cell; mAb, monoclonal antibody; MPO, myeloperoxidase; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PMN, polymorphonuclear cell; TNF, tumour necrosis factor; TNBS, 2,4,6-trinitrobenzene sulphonic acid; Treg, regulatory T cells

Related Article

Digest

Robin Spiller and Alastair Watson
Gut 2007 56: 1. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				N. Sugimoto, T. Rui, M. Yang, S. Bharwani, O. Handa, N. Yoshida, T. Yoshikawa, and P. R. Kvietys Points of Control Exerted along the Macrophage-Endothelial Cell-Polymorphonuclear Neutrophil Axis by PECAM-1 in the Innate Immune Response of Acute Colonic Inflammation J. Immunol., August 1, 2008; 181(3): 2145 - 2154. [Abstract] [Full Text] [PDF]

				Z. Zhou, X. Song, A. Berezov, G. Zhang, Y. Li, H. Zhang, R. Murali, B. Li, and M. I. Greene Human glucocorticoid-induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states PNAS, April 8, 2008; 105(14): 5465 - 5470. [Abstract] [Full Text] [PDF]

				S. Ronchetti, G. Nocentini, R. Bianchini, L. T. Krausz, G. Migliorati, and C. Riccardi Glucocorticoid-Induced TNFR-Related Protein Lowers the Threshold of CD28 Costimulation in CD8+ T Cells J. Immunol., November 1, 2007; 179(9): 5916 - 5926. [Abstract] [Full Text] [PDF]

				G. NOCENTINI, S. CUZZOCREA, R. BIANCHINI, E. MAZZON, and C. RICCARDI Modulation of Acute and Chronic Inflammation of the Lung by GITR and its Ligand Ann. N.Y. Acad. Sci., June 1, 2007; 1107(1): 380 - 391. [Abstract] [Full Text] [PDF]