The last two authors are joint senior authors on this work.
Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-β-deficient mice†
Article first published online: 29 OCT 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 1, pages 85–93, January 2012
How to Cite
Hardenberg, G., Yao, Y., Piccirillo, C. A., Levings, M. K. and Steiner, T. S. (2012), Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-β-deficient mice. Inflamm Bowel Dis, 18: 85–93. doi: 10.1002/ibd.21738
Supported by a new emerging team grant on IBD from the Canadian Institutes for Health Research (IIN 84037) and a Grant-in-Aid of research from the Crohn's and Colitis Foundation of Canada. G.H. holds a Michael Smith Foundation for Health Research (MSFHR) postdoctoral fellowship, Y.Y. is supported by a CIHR Transplantation Research Award, MKL holds a Canada Research Chair in Transplantation. C.A.P. holds a Canada Research Chair in Immune Regulation. Core support for flow cytometry sorting provided by Lixin Xu was funded by the Immunity and Infection Research Centre MSFHR Research Unit.
- Issue published online: 11 DEC 2011
- Article first published online: 29 OCT 2011
- Manuscript Accepted: 19 MAR 2011
- Manuscript Received: 7 MAR 2011
- T cells;
Toll-like receptor 5 (TLR5) is implicated in the innate and adaptive immune responses that are associated with inflammatory bowel disease (IBD). In humans TLR5 is expressed on CD4+ T cells and costimulation with flagellin potentiates effector and regulatory T cell responses. The aim of this study was to determine the role of TLR5 in CD4+ T cell subsets versus other cells in induction of disease in a model of T cell-dependent colitis.
TLR5 expression on CD4+ T cells was assessed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Wildtype (WT) or TLR5-deficient (5−/−) CD4+ T conventional cells (Tconv) and T regulatory cells (Treg) were compared for their ability to induce and suppress T cell transfer colitis, respectively. In addition, the role of TLR5 expression in recipient mice was analyzed.
TLR5 is preferentially expressed on mouse Treg compared to Tconv, although expression levels were low. The colitogenic capacity of WT and 5−/− Tconv was found to be similar and Treg from WT or 5−/− donor animals both prevented T cell transfer colitis in TLR-competent hosts. TLR5 deficiency in recipient mice, however, did affect the disease process, as T cell receptor-β (TCRβ) 5−/− recipients had decreased weight loss compared to TCRβ recipient mice when WT Tconv were used.
TLR5 expression on T cells is not required for induction of or protection from T cell-dependent colitis. Expression of TLR5 in non-T cells has a pathogenic role, since TLR5 deficiency in recipient mice protects against weight loss induced by WT T cells. (Inflamm Bowel Dis 2011;)