Genetic variation within TLR10 is associated with Crohn's disease in a New Zealand population

Morgan, Angharad R.; Lam, Wen-Jiun; Han, Dawei; Fraser, Alan G.; Ferguson, Lynnette R.

doi:10.1016/j.humimm.2012.01.015

Cited by 35 publications

(19 citation statements)

References 23 publications

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“…Some of the SNPs associated with CD in this cohort have been reported elsewhere [23,26,27,28], whilst others do not appear to have been reported. Here we focus on the gene-serum selenium interaction on CD.…”

Section: Discussionmentioning

confidence: 80%

Selenium, Selenoprotein Genes and Crohn’s Disease in a Case-Control Population from Auckland, New Zealand

et al. 2012

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New Zealand has one of the highest incidence rates of Crohn’s Disease (CD), whilst the serum selenium status of New Zealanders is amongst the lowest in the world. A prospective case-control study in Auckland, New Zealand considered serum selenium as a potential CD risk factor. Serum selenium levels were significantly lower in CD patients compared to controls (101.8 ± 1.02 vs. 111.1 ± 1.01 ng/mL) (p = 5.91 × 10−8). Recent detailed studies in the United Kingdom have suggested an optimal serum level around 122 ng/mL, making the average CD patient in New Zealand selenium deficient. Of the 29 single nucleotide polymorphisms (SNPs) tested, 13 were found to significantly interact with serum selenium on CD. After adjustment for multiple testing, a significant interaction with serum selenium on CD was found for three SNPs, namely rs17529609 and rs7901303 in the gene SEPHS1, and rs1553153 in the gene SEPSECS. These three SNPs have not been reported elsewhere as being significantly associated with selenium or CD. It is unclear as to whether lower selenium levels are a cause or an effect of the disease.

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Section: Discussionmentioning

confidence: 80%

Selenium, Selenoprotein Genes and Crohn’s Disease in a Case-Control Population from Auckland, New Zealand

et al. 2012

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“…4,7 Currently, there is no natural ligand identified for TLR10. 17,18 It is well documented that IL-1b is one of the crucial cytokines involved in innate immune memory and in the induction of trained immunity. 6,7 Surprisingly, TLR10 does not induce the classical TLR downstream signaling pathway, even though it has been shown that it can associate with myeloid differentiation primary response 88 6 and protein kinase B.…”

Section: Introductionmentioning

confidence: 99%

“…9,12,13 Moreover, polymorphisms in TLR10 have been associated with various diseases, including complicated skin and skin-structure infections, 14 tuberculosis, 15 prostate cancer 16 and Crohn's disease. 17,18 It is well documented that IL-1b is one of the crucial cytokines involved in innate immune memory and in the induction of trained immunity. 19 Trained immunity is a process in which human innate immune cells such as monocytes can undergo extensive metabolic and epigenetic reprogramming upon certain infections or vaccinations, resulting not only in long-term enhanced immune responses and resistance to heterologous infections, 20 but also in induction of maladaptive immune responses in inflammatory diseases when cells are stimulated by endogenous ligands.…”

Section: Introductionmentioning

confidence: 99%

The role of Toll‐like receptor 10 in modulation of trained immunity

et al. 2019

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Toll-like receptor 10 (TLR10) is the only member of the human Toll-like receptor family with an inhibitory function on the induction of innate immune responses and inflammation. However, its role in the modulation of trained immunity (innate immune memory) is unknown. In the present study, we assessed whether TLR10 modulates the induction of trained immunity induced by b-glucan or bacillus Calmette-Gu erin (BCG). Interleukin 10 receptor antagonist production was increased upon activation of TLR10 ex vivo after BCG vaccination, and TLR10 protein expression on monocytes was increased after BCG vaccination, whereas anti-TLR10 antibodies did not significantly modulate b-glucan or BCG-induced trained immunity in vitro. A known immunomodulatory TLR10 missense single-nucleotide polymorphism (rs11096957) influenced trained immunity responses by b-glucan or BCG in vitro. However, the in vivo induction of trained immunity by BCG vaccination was not influenced by TLR10 polymorphisms. In conclusion, TLR10 has a limited, non-essential impact on the induction of trained immunity in humans.

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“…Upon activation, TLR10 forms a homo-or a hetero-dimer with TLR1 or TLR2 and transmits intracellular signal by recruiting myeloid differentiation factor (MyD)-88 to the activated receptor complex [4]. Genetic polymorphisms in the human TLR10 have been linked to various diseases such as asthma, bladder and nasopharyngeal carcinomas, and Crohn’s disease which indicates a functional role of TLR10 in these inflammatory diseases [5-8] as well as in the innate immune response to influenza virus infection [1]. …”

Section: Introductionmentioning

confidence: 99%

Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

Sindhu

Akhter

Kochumon

et al. 2018

Cell Physiol Biochem

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Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H₂O₂) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H₂O₂-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation.

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Genetic variation within TLR10 is associated with Crohn's disease in a New Zealand population

Cited by 35 publications

References 23 publications

Selenium, Selenoprotein Genes and Crohn’s Disease in a Case-Control Population from Auckland, New Zealand

Selenium, Selenoprotein Genes and Crohn’s Disease in a Case-Control Population from Auckland, New Zealand

The role of Toll‐like receptor 10 in modulation of trained immunity

Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

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