Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population

Wang, Chin Man; Chang, Su Wei; Wu, Yeong Jian Jan; Lin, Jing; Ho, Huei-Huang; Chou, Tse Chih; Yang, Bing; Wu, Jianming; Chen, Ji Yih

doi:10.1038/srep03792

Cited by 98 publications

(79 citation statements)

References 70 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hsin-Yi et al have shown that rs3775296, located in the 5′-UTR of TLR3, is associated with elevated TLR3 expression and susceptibility to knee osteoarthritis in a Chinese Han population [31]. Moreover, the rs3775296-T allele was associated with photosensitivity and anemia of system lupus erythematosus in females in a Taiwanese population [32]. However, in the present study, we failed to observe an association between rs3775296 and PE.…”

Section: Discussioncontrasting

confidence: 54%

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia

Chen

Wang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Accumulating evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with exaggerated activation of the innate immune system plays a critical role in the development of preeclampsia (PE). In this study, we investigated whether polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with susceptibility to PE in the Chinese Han population. Methods: We recruited 987 PE patients and 1227 healthy pregnant women. Two polymorphisms (rs3775291 and rs3775296) located in TLR3 were genotyped by TaqMan allelic discrimination real-time PCR. The association between the genotype or allele frequencies and PE was examined using chi-square tests. Clinical data were compared between cases and controls using Student's t test. Results: No significant difference was determined in the genetic distribution of rs3775291 and rs3775296 between cases and controls. There were also no significant differences in the genotype and allele frequencies of either SNP between healthy pregnant women and patients with late or early onset PE, or with mild or severe PE. Conclusion: Although this is the first study of the association between TLR3 polymorphisms and preeclampsia, we found that TLR3 polymorphisms are unlikely to play a significant role in the development of preeclampsia in the Chinese Han population.

show abstract

Section: Discussioncontrasting

confidence: 54%

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia

Chen

Wang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Nucleic acids are capable of activating a cohort of endosomal receptors, including but not limited to TRL7 and TLR9 (48,49), thus rendering these compounds partially effective in multifaceted autoimmune disorders that rely on multiple types of receptors. Moreover, TLR7 gene mutations play an important role in disease severity, and any therapies that directly target these receptors could potentially fail due to decreased mutant receptor binding (50)(51)(52). Our strategy does not rely on receptor binding, therefore, addressing a number of these concerns.…”

Section: Discussionmentioning

confidence: 99%

Scavenging nucleic acid debris to combat autoimmunity and infectious disease

Holl

Shumansky

Borst

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal’s ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.

show abstract

“…The Leu180 allele of MAL/TIRAP polymorphism indicated reduced susceptibility to SLE regarded as a protective factor against the development of SLE [60] . 12 The single nucleotide polymorphisms (SNPs) of TLR7 rs3853839, TLR8 rs3764880, together with TLR9 rs351240 have been shown to increase the risk of SLE in an Asian population [61,62].…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

“…The single nucleotide polymorphisms (SNPs) of TLR7 rs3853839, TLR8 rs3764880, together with TLR9 rs351240 have been shown to increase the risk of SLE in an Asian population [61,62].…”

mentioning

confidence: 99%

Toll-Like Receptor Pathways in Autoimmune Diseases

Chen

Szodoray

Zeher

2015

Clinic Rev Allerg Immunol

242

177

View full text Add to dashboard Cite

Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen.Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location；the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. Particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathways regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. KEYWORDS:Toll-like receptors (TLRs); autoimmune disease; IL-1 receptor associated kinase (IRAK); TNF receptor associated factor (TRAF); Suppressor of cytokine signaling (SOCS) 3 Autoimmune diseases are characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Even though the accurate etiology and pathogenesis of the majority of these diseases are still not clear, complex elements, including genetic, environmental, hormonal factors may provoke the autoimmune processes leading to the development of the disease.Concerning the role of derailed immune responses in the pathogenesis, aberrant processes both in the innate and adaptive immune system have been shown to participate in the disease initiation and perpetuation [1]. Within these processes, numerous studies have been demonstrated that Toll-like receptors (TLRs) have an essential role in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. [2,3]. Toll-like receptorsThe innate immune system is the first line of host defense mechanisms against invading microorganisms and forms the basis of the development of adaptive immunity. Host cells express diverse pattern recognition receptors (PRRs) include toll-like receptors (TLRs), C-type lectin-like receptors (CL...

show abstract

Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population

Cited by 98 publications

References 70 publications

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia

Scavenging nucleic acid debris to combat autoimmunity and infectious disease

Toll-Like Receptor Pathways in Autoimmune Diseases

Contact Info

Product

Resources

About