TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses

Hess, Nicholas J; Jiang, Siwei; Li, Xinyan; Guan, Yue; Tapping, Richard I.

doi:10.4049/jimmunol.1601335

Cited by 44 publications

(33 citation statements)

References 37 publications

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“…8a ). At the single cell level, we observed that TLR10 was only expressed by HLA + B cells, indicating that TLR10 has a functional role within the B cell lineage 36 . In contrast, TLR8 was significantly elevated in all RA monocyte subsets.…”

Section: Resultsmentioning

confidence: 88%

Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry

Zhang

Wei

Slowikowski

et al. 2018

Preprint

169

371

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Wei, Slowikowski, Fonseka, Rao et al A single cell map of the RA joint Abstract 78 To define the cell populations in rheumatoid arthritis (RA) driving joint inflammation, we applied 79 single-cell RNA-seq (scRNA-seq), mass cytometry, bulk RNA-seq, and flow cytometry to sorted 80 T cells, B cells, monocytes, and fibroblasts from 51 synovial tissue RA and osteoarthritis (OA) 81 patient samples. Utilizing an integrated computational strategy based on canonical correlation 82 analysis to 5,452 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass 83 cytometry and transcriptomics together revealed cell states expanded in RA synovia: 84 THY1 + HLA high sublining fibroblasts (OR=33.8), IL1B + pro-inflammatory monocytes (OR=7.8), 85 CD11c + T-bet + autoimmune-associated B cells (OR=5.7), and PD-1 + Tph/Tfh (OR=3.0). We also 86 defined CD8 + T cell subsets characterized by GZMK + , GZMB + , and GNLY + expression. Using 87 bulk and single-cell data, we mapped inflammatory mediators to source cell populations, for 88 example attributing IL6 production to THY1 + HLA high fibroblasts and naïve B cells, and IL1B to 89 pro-inflammatory monocytes. These populations are potentially key mediators of RA 90 pathogenesis. 91 92 93 94 95 96 97 98 99 100

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Section: Resultsmentioning

confidence: 88%

Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry

Zhang

Wei

Slowikowski

et al. 2018

Preprint

169

371

View full text Add to dashboard Cite

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“…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%

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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“…TLR10 remains an orphan receptor without a confirmed ligand, signaling pathway, or biological function. However, it is widely expressed in lymphoid tissues including the spleen, lymph node, thymus, and tonsils as well as a number of leukocyte subtypes, especially B cells ( 13 ). This expression pattern suggests that TLR10 has an immune function similar to other TLRs.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series

et al. 2018

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BackgroundThe toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB).MethodsUsing a self-validating case–control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method. Three genetic models (additive, dominant, and recessive) as well as multiple-SNP score analyses were used to evaluate the risk of TB associated with the TLR10 SNPs.ResultsBy comparing TB patients with healthy controls, we observed two SNPs (rs11466617 and rs4129009) that were associated with decreased risk of TB in the Tibetan population, but did not in the Chinese Han population. Further analysis demonstrated that the rs11466617 Chengdu cohort genotype served as a protective factor against the progression of latent TB infection (LTBI) to active TB under the recessive model. None of the SNPs were significantly different in comparisons of TB-uninfected people with LTBI individuals. Additionally, when the underlying four TB-associated loci were considered together in a multiple-SNP score analysis, we observed an allele dose-dependent decrease in TB risk in Tibetans.ConclusionVariants of TLR10 may show an ethnic specificity on susceptibility to TB in Tibetan individuals. rs11466617 affected the susceptibility to progress from LTBI to active TB disease, but was not associated with the establishment of LTBI after M. tuberculosis exposure. More studies are needed to verify this genetic epidemiological result and unravel the role of TLR10 SNPs in the pathogenesis of TB.

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TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses

Cited by 44 publications

References 37 publications

Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry

Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry

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

Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series

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