Does TLR2 regulate intestinal inflammation?

Mowat, Allan McI

doi:10.1002/eji.200940232

Cited by 11 publications

(9 citation statements)

References 21 publications

(31 reference statements)

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“…In contrast to the above findings, which have alluded to the important role of TLR signaling in T effector and regulatory functions, some reports indicate that TLR-costimulation in T cells leads to enhanced autoreactivity in certain conditions, such as autoimmune arthritis, systemic lupus erythematosus (SLE) and multiple sclerosis (Himmel et al 2008;Marta 2009;Mowat 2010). For example, a microbial lipoprotein, Lip-Osp A from Borrelia burgdorferi (the causative agent of Lyme disease), was shown to induce a TLR2-dependent autoimmune arthritis in C57BL/6 mice (Sobek et al 2004).…”

Section: Tlr-costimulation In T Cells and Autoimmunitymentioning

confidence: 87%

Insights into the role of Toll-like receptors in modulation of T cell responses

2010

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The innate immune receptors, such as Toll-like receptors (TLRs), are intimately involved in the early sensing of invading microorganisms or their structural components. Engagement of TLRs with their ligands results in activation of several downstream intracellular pathways leading to activation of innate and adaptive immune system cells. It was initially thought that TLRs are primarily expressed by antigen-presenting cells (APCs), such as macrophages and dendritic cells, and that interactions between microbial ligands and TLRs in these cells will indirectly result in activation of cells of the adaptive immune system, especially T cells. However, it has now become evident that TLRs are also expressed by various T cell subsets, such as conventional αβT cells, regulatory T cells, and γδT cells as well as natural killer T cells. Importantly, it appears that at least in some of these T cell subsets, TLRs are functionally active, because stimulation of these cells with TLR agonists in the absence of APCs results in exertion of effector or regulatory functions of T cells. The present review attempts to summarize the recent findings related to TLR expression in different T cell subsets and the direct role of TLRs in the induction and regulation of T cell responses, including those responses that occur at mucosal surfaces. In addition, the potential use of TLR agonists for steering T cell responses as a prophylactic or therapeutic strategy in the context of infectious, allergic or autoimmune diseases is explored.

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Section: Tlr-costimulation In T Cells and Autoimmunitymentioning

confidence: 87%

Insights into the role of Toll-like receptors in modulation of T cell responses

2010

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“…Namely, whole TABLE 3. Bacterial species with significant difference in abundance between Tlr2 Ϫ/Ϫ (TLR- [1][2][3][4][5] and WT (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) genomic interrogation of DNA methylation changes showed that ϳ1.4% of the colonocyte genome is modified epigenetically in Tlr2 Ϫ/Ϫ mice. These changes were associated more with CpG islands, gene promoters, DNase I hypersensitive regions, and CTCF-binding sites than control regions.…”

Section: Discussionmentioning

confidence: 98%

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll‐like receptor 2‐knockout mice

et al. 2011

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The connection between intestinal microbiota and host physiology is increasingly becoming recognized. The details of this dynamic interaction, however, remain to be explored. Toll-like receptor 2 (Tlr2) is important for its role in bacterial recognition, intestinal inflammation, and obesity-related metabolic changes. Therefore, we sought to determine the epigenomic and metagenomic consequences of Tlr2 deficiency in the colonic mucosa of mice to gain insights into biological pathways that shape the interface between the gut microbiota and the mammalian host. Colonic mucosa from wild type (WT) and Tlr2(-/-) C57BL/6 mice was interrogated by microarrays specific for DNA methylation and gene expression. The mucosal microbiome was studied by next-generation pyrosequencing of bacterial 16S rRNA. The expression of genes involved in immune processes was significantly modified by the absence of Tlr2, a number of which correlated with DNA methylation changes. The epigenomic and transcriptomic modifications associated with alteration in mucosal microbial composition. Several bacterial species, including members of the Firmicutes were significantly different in abundance between WT and Tlr2(-/-) animals. This manuscript highlights the intimate interrelationships between expression of immune-related genes and immunity pathways in the host with compositional and functional differences of the mammalian microbiome.

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“…However, in chronic intestinal inflammation, such as that induced by adoptive transfer of naïve CD4 + T cells into mice lacking adaptive immunity (RAG1-deficient mice), TLR2 signaling does not affect gut pathology 26 . Therefore, TLR2 signaling may confer protection against acute mechanical injury through maintenance of tight junction integrity while having minimal effects on regulation of sustained inflammatory processes.…”

Section: Tlr2 and Its Co-receptors Tlr1 And Tlr6mentioning

confidence: 99%

Toll-like receptor signaling and regulation of intestinal immunity

2013

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The intestine is a complex organ that must maintain tolerance to innocuous food antigens and commensal microbiota while being also able to mount inflammatory responses against invading pathogenic microorganisms. The ability to restrain tolerogenic responses while permitting inflammatory responses requires communication between commensal bacteria, intestinal epithelial cells and immune cells. Disruption or improper signaling between any of these factors may lead to uncontrolled inflammation and the development of inflammatory diseases. Toll-like receptors (TLR) recognize conserved molecular motifs of microorganisms and, not surprisingly, are important for maintaining tolerance to commensal microbiota, as well as inducing inflammation against pathogens. Perturbations in individual TLR signaling can lead to a number of different outcomes and illustrate a system of regulation within the intestine in which each TLR plays a largely non-redundant role in mucosal immunity. This review will discuss recent findings on the roles of individual TLRs and intestinal homeostasis.

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Does TLR2 regulate intestinal inflammation?

Cited by 11 publications

References 21 publications

Insights into the role of Toll-like receptors in modulation of T cell responses

Insights into the role of Toll-like receptors in modulation of T cell responses

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll‐like receptor 2‐knockout mice

Toll-like receptor signaling and regulation of intestinal immunity

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