Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma

Tantisira, Kelan G.; Klimecki, Walter T.; Lazarus, Ross; Palmer, Lyle J.; Raby, Benjamin A.; Kwiatkowski, David J.; Silverman, Edwin K.; Vercelli, Donata; Martínez, Fernando D.; Weiss, Scott T.

doi:10.1038/sj.gene.6364096

Cited by 82 publications

(54 citation statements)

References 22 publications

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“…The epidemiological observation that the modified exposure to microbial particles in westernised areas is associated with a reduced prevalence of atopic diseases, the so-called ''hygiene hypothesis'', may thus be explained by the reduced production of IL-12 shifting the immune responses to a predominantly Th2 type. This hypothesis was supported by recent findings that genetic variations in the TLR2, TLR4, TLR6 and TLR10 genes were associated with atopy in children [70][71][72][73][74].…”

Section: Impact Of Innate Immunity On T-cell Differentiation and Devesupporting

confidence: 74%

T-cell co-stimulatory molecules: their role in allergic immune reactions

Kallinich¹,

Beier²,

Wahn³

et al. 2007

European Respiratory Journal

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The development of allergic diseases, such as allergic asthma, depends upon the initiation and maintenance of T-helper cell type-2-skewed allergen-specific immune reactions. Although it is clear that susceptibility to this process is under genetic and environmental control, the fine-tuning and regulation of the type-2 T-helper cell immune response is not yet fully understood. In this second article in the present series, current understanding regarding the involvement of T-cells and antigen-presenting cells is summarised, with emphasis on the interaction between these two types of immune regulatory cells by means of co-stimulatory molecules.

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Section: Impact Of Innate Immunity On T-cell Differentiation and Devesupporting

confidence: 74%

T-cell co-stimulatory molecules: their role in allergic immune reactions

Kallinich¹,

Beier²,

Wahn³

et al. 2007

European Respiratory Journal

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“…Of the 10 known human TLR members, TLR6 is 1 of 2 (the other is TLR10) TLRs found to have strong associations with asthma susceptibility. Independent studies in both adult (14,15) and pediatric (17) patient cohorts have confirmed that variations in TLR6 have relevance to the pathogenesis of asthma. The most recent studies by Kormann and colleagues (17) revealed that protective polymorphisms in TLR6 promoted Th1-type cytokine expression.…”

Section: Discussionmentioning

confidence: 98%

“…Previous clinical studies have addressed the presence of TLR6 polymorphisms in clinical asthma (14,15,17) and invasive aspergillosis following stem cell transplant (18), and all of these studies suggested that TLR6 activity provides an important protective role in the lung. In the present study, whole-lung samples from patients with severe asthma exhibited strong TLR6 expression, particularly in mononuclear and alveolar epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Signaling through both complexes leads to NF-κB activation and cytokine generation (13). The putative role of TLR6 during clinical asthma is still unknown, but clinical studies have indicated that single nucleotide polymorphisms in TLR6 have a role in the protection from asthma (14)(15)(16). More recently, protective effects of TLR6 polymorphisms in asthma were associated with increased expression and greater mononuclear cell generation of Th1-type cytokines (17).…”

Section: Introductionmentioning

confidence: 99%

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The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A

Moreira¹,

Cavassani²,

Ismailoglu³

et al. 2011

J. Clin. Invest.

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TLRs are a family of receptors that mediate immune system pathogen recognition. In the respiratory system, TLR activation has both beneficial and deleterious effects in asthma. For example, clinical data indicate that TLR6 activation exerts protective effects in asthma. Here, we explored the mechanism or mechanisms through which TLR6 mediates this effect using mouse models of Aspergillus fumigatus-induced and house dust mite antigen-induced (HDM antigen-induced) chronic asthma. Tlr6 -/-mice with fungal-or HDM antigen-induced asthma exhibited substantially increased airway hyperresponsiveness, inflammation, and remodeling compared with WT asthmatic groups. Surprisingly, whole-lung levels of IL-23 and IL-17 were markedly lower in Tlr6 -/-versus WT asthmatic mice. Tlr6 -/-DCs generated less IL-23 upon activation with lipopolysaccharide, zymosan, or curdlan. Impaired IL-23 generation in Tlr6 -/-mice also corresponded with lower levels of expression of the pathogen-recognition receptor dectin-1 and expansion of Th17 cells both in vivo and in vitro.

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“…15 Four mRNA isoforms have been identified, but all encode the same protein (http://www.ncbi.nlm.nih.gov/sites/entrez). Variations within the TLR10-TLR1-TLR6 gene cluster have been associated with several diseases, including asthma, 16,17 prostate cancer, 18 nasopharyngeal carcinoma, 19 non-Hodgkin lymphoma, 20 Lyme disease 21 and atherogenesis. 22 However, association between the TLR10-TLR1-TLR6 gene cluster and CD has not been yet studied.…”

Section: Introductionmentioning

confidence: 99%

Association of Toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2

et al. 2011

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Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10 GGGG ) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio ¼ 1.89, P-value ¼ 0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10 GGGG haplotype (P c o0.0001). The interaction gain attributed to the combination of both genes was negative (IG ¼ À2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes.

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Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma

Cited by 82 publications

References 22 publications

T-cell co-stimulatory molecules: their role in allergic immune reactions

T-cell co-stimulatory molecules: their role in allergic immune reactions

The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A

Association of Toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2

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