TLR10 suppresses the activation and differentiation of monocytes with effects on DC-mediated adaptive immune responses

Hess, Nicholas J; Felicelli, Christopher; Grage, Jennifer; Tapping, Richard I.

doi:10.1189/jlb.3a1116-492r

Cited by 43 publications

(45 citation statements)

References 29 publications

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“…4,7 We investigated TLR10 expression in monocytes stimulated for 24 hr with different stimuli. 4,7 We investigated TLR10 expression in monocytes stimulated for 24 hr with different stimuli.…”

Section: Tlr10 Expression On the Cell Surface Of Monocytes Increases mentioning

confidence: 99%

“…TLRs activate intracellular signaling pathways upon recognition of pathogen-associated molecular patterns, which results in activation of the innate immune response. 4,7 Currently, there is no natural ligand identified for TLR10. 1,2 Human TLR10 was discovered in 2001, 3 and is located on chromosome 4 within the TLR2 gene cluster, together with TLR1 and TLR6.…”

Section: Introductionmentioning

confidence: 99%

“…TLR10 is structurally similar to the other TLR family members and is phylogenetically most related to TLR1 and TLR6. 4,7,10,11 TLR10 single nucleotide polymorphisms (SNPs) strongly influence pro-inflammatory cytokine production in humans, and in hTLR10 transgenic mice, significantly lower interleukin-6 (IL-6) and KC (mouse analog of human IL-8) concentrations in plasma were found compared with wild-type mice. 4,7 Currently, there is no natural ligand identified for TLR10.…”

Section: Introductionmentioning

confidence: 99%

“…TLR10 is structurally similar to the other TLR family members and is phylogenetically most related to TLR1 and TLR6. 3 TLR10 mRNA is highly expressed in lymphoid tissues, 3 and is expressed in different immune cells, including B cells, dendritic cells, [4][5][6] and monocytes. 4,7 Currently, there is no natural ligand identified for TLR10.…”

Section: Introductionmentioning

confidence: 99%

“…7 Although it was initially reported that TLR10 had a pro-inflammatory function, 8,9 the majority of reports have demonstrated anti-inflammatory properties of TLR10. 4,7,10,11 TLR10 single nucleotide polymorphisms (SNPs) strongly influence pro-inflammatory cytokine production in humans, and in hTLR10 transgenic mice, significantly lower interleukin-6 (IL-6) and KC (mouse analog of human IL-8) concentrations in plasma were found compared with wild-type mice. 7 TLR10 has been shown to be involved in the induction of innate immune responses to influenza and is involved in Helicobacter pylori infection.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Tlr10 Expression On the Cell Surface Of Monocytes Increases mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Effect of TLR10 (2322A/G, 720A/C, and 992T/A) polymorphisms on the pathogenesis of Crimean Congo hemorrhagic fever disease

Kızıldağ

Arslan

Özbilüm

et al. 2017

Journal of Medical Virology

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Crimean Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean Congo hemorrhagic fever virus (CCHFV). Toll-like receptors (TLRs) are type 1 transmembrane proteins of immune cells that play a critical role in innate and adaptive immunity. The present study first time aims to investigate the relation between TLR10 gene polymorphisms (720A/C, 992T/A, and 2322A/G), severity/non-severity, fatality/ non-fatality, and CCFH disease by using PCR-RFLP assay in a Turkish population.TLR10 720A/C polymorphism was determined to be statistically significant both genotype and allele frequency (P = 0,011, P = 0.015, respectively). TLR10 992T/A polymorphism was found statistically significant relationships between patient and control (P = 0.026) and individual with AA genotype have approximately three times greater risk than TT genotype (OR = 2.93). There was not a significant difference in 2322A/G genotype distribution (P = 0.152). There were also statistically significant associations between both TLR10 992T/A and 2322A/G polymorphism and patient mortality (P = 0.001 and P = 0.008, respectively). We have not found statistically any linkage among TLR10 haplotype, but individual AAA and GAT haplotype have higher risk than individual AAT haplotype (OR = 3.22, OR = 1.93, respectively). Consequently, this study shows that pathogenesis of CCHF disease is associated with the TLR10 720A/C and 992T/A polymorphisms. There is a statistically significant association in fatal/non-fatal patients with TLR10 720A/C and 992T/A. The TLR10 992AA genotype might increase and TLR10 720CC genotype might decrease susceptibility to pathogenesis of CCHF disease. TLR 10 polymorphisms may be also an important biomarker for CCHF susceptibility and fatality rate. K E Y W O R D SCrimean-Congo hemorrhagic fever virus, genetic polymorphism, TLR10

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Toll‐like receptor 10 controls TLR2‐induced cytokine production in monocytes from patients with Parkinson's disease

Sobrinho

Gomes

Silva

et al. 2021

J of Neuroscience Research

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Peripheral inflammation, particularly mediated by monocytes, can cause neuroinflammation in Parkinson's disease (PD). We investigated the mechanism of TLR2-induced cytokine impairment in peripheral monocytes from PD patients and the association between the presence of CD14 + TLR10 + monocytes and PD severity. Peripheral blood mononuclear cells from PD patients and healthy individuals were evaluated for TLR expression on monocyte subsets (CD14 and CD16 expression) using flow cytometry. Moreover, cytokines were evaluated using flow cytometry after stimulation with Pam 3 Cys (TLR2/TLR1 agonist) in the absence or presence of neutralizing antibodies to TLR10. The severity of PD was assessed using the unified PD rating scale (UPDRS) and motor activity, anxiety (BAI), depression (BDI), and fatigue (PD Fatigue Scale-16) scales. The frequency of CD14 + TLR10 + monocytes and expression intensity of TLR2 and TLR10 were higher in patients with PD than healthy individuals. The frequency of intermediate monocytes (CD14 ++ CD16 + ) was not significantly increased in patients with PD, but was the main monocyte subset expressing TLR10.The TLR2/TLR1-impaired cytokine production TNFα, in PD patients was reversed by neutralizing TLR10. The high frequency of total CD14 + TLR10 + monocytes was associated with a reduction in the severity of PD according to the evaluation of motor and nonmotor symptoms. Peripheral monocytes from patients with PD showed phenotypic and functional alterations. The expression of TLR10 on monocytes can protect against PD by controlling TLR2-induced cytokine production. Furthermore, data suggested that a low frequency of CD14 + TLR10 + monocytes indicates the severity of PD. The results identified new opportunities for the development of novel PD neuroprotective therapies.

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TLR10 suppresses the activation and differentiation of monocytes with effects on DC-mediated adaptive immune responses

Cited by 43 publications

References 29 publications

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

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

Effect of TLR10 (2322A/G, 720A/C, and 992T/A) polymorphisms on the pathogenesis of Crimean Congo hemorrhagic fever disease

Toll‐like receptor 10 controls TLR2‐induced cytokine production in monocytes from patients with Parkinson's disease

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