Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-β-deficient mice.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Surgery, University of British Columbia and Immunity in Health & Disease, Child and Family Research Institute, British Columbia Children's Hospital, Vancouver, Canada.
Gijs
G
Hardenberg
Yu
Y
Yao
Ciriaco A
CA
Piccirillo
Megan K
MK
Levings
Theodore S
TS
Steiner
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D003092:Colitis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*; D051198:Toll-Like Receptor 5 / Q000502:physiology*; D019282:Wasting Syndrome / Q000517:prevention & control*
D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051198:Toll-Like Receptor 5