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

Hardenberg, Gijs; Yao, Yu; Piccirillo, Ciriaco A.; Levings, Megan K.; Steiner, Theodore S.

doi:10.1002/ibd.21738

Cited by 13 publications

(7 citation statements)

References 48 publications

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“…Although our data are supported by a recent report on a protective role for TLR5 defi ciency for colitis development in a T cell transfer model [54], another study reported, in contrast, a potentiating effect of the TLR5 agonist fl agellin on induction, expansion and suppressive activity of Foxp3 + Tregs [28,52]. While differing compositions of commensal enteric communities between laboratories might explain these contrasting results, our data clearly show that microbiota-driven proliferation of conventional CD4 + T cells and Foxp3 + Tregs can occur in the absence of TLR-signaling.…”

Section: Discussionsupporting

confidence: 89%

Commensal microbiota drive proliferation of conventional and Foxp3⁺Regulatory CD4⁺T cells in mesenteric lymph nodes and Peyer's patches

Cording¹,

Fleissner²,

Heimesaat³

et al. 2013

European Journal of Microbiology and Immunology

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Compelling evidence demonstrates that intestinal commensal microbiota modulate conventional and regulatory T cell (Treg) responses that are required for effective host defence against pathogens and avoidance of autoimmunity and other immunopathologic conditions. Here, we investigated the contribution of the commensal microbiota and Toll-like receptor (TLR) signaling to homeostasis of Foxp3− conventional CD4 + T cells and Foxp3 + Tregs. Upon long-term antibiotics treatment, we observed a significant reduction of conventional CD4 + T cell proliferation in a systemic manner, whereas Foxp3 + Treg proliferation was locally impaired in gut-draining mesenteric lymph nodes and Peyer's patches. The proliferative response to microbial components was not mediated by TLRs as MyD88-and various TLR-deficient mice displayed normal or even increased conventional T cell and Foxp3 + Treg proliferation. Thus, commensal microbiota-derived stimuli support cycling of both conventional CD4 + T cells and Foxp3 + Tregs with TLR-mediated recognition of bacterial components not being the major mechanism controlling microbiota-driven T cell homeostasis.

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Section: Discussionsupporting

confidence: 89%

Commensal microbiota drive proliferation of conventional and Foxp3⁺Regulatory CD4⁺T cells in mesenteric lymph nodes and Peyer's patches

Cording¹,

Fleissner²,

Heimesaat³

et al. 2013

European Journal of Microbiology and Immunology

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“…Lamina propria mononuclear cells (LPMC) were isolated as previously described (28). Briefly, colons and ceca were collected, washed, and placed in a shaking incubator at 37°C in RPMI 1640 containing 10% heatinactivated FCS and 5 mM EDTA.…”

Section: Methodsmentioning

confidence: 99%

Active vitamin D (1,25-dihydroxyvitamin D₃) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses

Ryz

Patterson

Zhang

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)(2)D(3) to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)(2)D(3) treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)(2)D(3)-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)(2)D(3)-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)(2)D(3) suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.

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“…CpG, a TLR9 ligand, has also been reported to undermine Treg induction as well as suppression in a MyD88‐dependent loss of Treg function . In contrast, TLR5 ligation with flagellin has been reported to enhance Foxp3 expression and Treg function , although another study found TLR5 −/− Tregs were functional in vivo and potential immune suppressive effects were originated on other cell types .…”

Section: Treg Stability Is Regulated By Numerous External Inputsmentioning

confidence: 99%

Treg functional stability and its responsiveness to the microenvironment

Barbi

Pardoll

Fan

2014

Immunological Reviews

203

151

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Summary Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability.

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

Abstract: 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.

Cited by 13 publications

References 48 publications

Commensal microbiota drive proliferation of conventional and Foxp3⁺Regulatory CD4⁺T cells in mesenteric lymph nodes and Peyer's patches

Commensal microbiota drive proliferation of conventional and Foxp3⁺Regulatory CD4⁺T cells in mesenteric lymph nodes and Peyer's patches

Active vitamin D (1,25-dihydroxyvitamin D₃) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses

Treg functional stability and its responsiveness to the microenvironment

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

Abstract: 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.

Cited by 13 publications

References 48 publications

Commensal microbiota drive proliferation of conventional and Foxp3+Regulatory CD4+T cells in mesenteric lymph nodes and Peyer's patches

Commensal microbiota drive proliferation of conventional and Foxp3+Regulatory CD4+T cells in mesenteric lymph nodes and Peyer's patches

Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses

Treg functional stability and its responsiveness to the microenvironment

Contact Info

Product

Resources

About

Commensal microbiota drive proliferation of conventional and Foxp3⁺Regulatory CD4⁺T cells in mesenteric lymph nodes and Peyer's patches

Commensal microbiota drive proliferation of conventional and Foxp3⁺Regulatory CD4⁺T cells in mesenteric lymph nodes and Peyer's patches

Active vitamin D (1,25-dihydroxyvitamin D₃) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses