Synergistic benefit in inflammatory arthritis by targeting IκB kinase ϵ and interferon β

Objectives:The IκB kinase (IKK)-related kinase IKKϵ regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKϵ in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) β therapy in passive murine K/BxN arthritis.Methods:IKKϵ–/–, IFNα∼βR–/– and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFNβ, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array.Results:Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFNα∼βR had an accelerated course of arthritis, and did not respond to poly(I:C). IKKϵ null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFNβ that were ineffective in wild type mice significantly decreased clinical arthritis in IKKϵ null mice. Articular chemokine gene expression was reduced in the IKKϵ–/– mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFNβ-treated IKKϵ–/– mice.Conclusions:Subtherapeutic doses of IFNβ enhance the anti-inflammatory effects of IKKϵ deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFNβ and an IKKϵ inhibitor might improve efficacy of either agent alone and offers a novel approach to RA.

Download Full-text

SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response

Cells ◽

10.3390/cells10030530 ◽

2021 ◽

Vol 10 (3) ◽

pp. 530

Author(s):

Soo Jin Oh ◽

Ok Sarah Shin

Keyword(s):

Nucleocapsid Protein ◽

Nuclear Translocation ◽

Nonstructural Protein ◽

Poly I:C ◽

Interferon Response ◽

Type I ◽

Antiviral Immune Response ◽

N Protein ◽

Nonstructural Protein 1 ◽

Polycytidylic Acid

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.

Download Full-text

Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation

Molecular and Cellular Biology ◽

10.1128/mcb.11.1.47-54.1991 ◽

1991 ◽

Vol 11 (1) ◽

pp. 47-54

Author(s):

H Chan ◽

S Hartung ◽

M Breindl

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Chromatin Structure ◽

Transcriptional Activity ◽

Xenopus Laevis Oocytes ◽

Regulatory Sequences ◽

Type I ◽

Wild Type ◽

Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

Download Full-text

Differential Effects of Low-Dose and High-Dose Beta-Carotene Supplementation on the Signs of Photoaging and Type I Procollagen Gene Expression in Human Skin in vivo

Dermatology ◽

10.1159/000305548 ◽

2010 ◽

Vol 221 (2) ◽

pp. 160-171 ◽

Cited By ~ 27

Author(s):

Soyun Cho ◽

Dong Hun Lee ◽

Chong-Hyun Won ◽

Sang Min Kim ◽

Serah Lee ◽

...

Keyword(s):

Gene Expression ◽

Human Skin ◽

Low Dose ◽

Beta Carotene ◽

High Dose ◽

Type I ◽

Differential Effects ◽

Type I Procollagen

Download Full-text

HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections

Journal of Experimental Medicine ◽

10.1084/jem.20161630 ◽

2017 ◽

Vol 214 (11) ◽

pp. 3263-3277 ◽

Cited By ~ 12

Author(s):

Lei Sun ◽

Zhengfan Jiang ◽

Victoria A. Acosta-Rodriguez ◽

Michael Berger ◽

Xin Du ◽

...

Keyword(s):

Viral Infections ◽

Poly I:C ◽

Type I ◽

Induced Mutations ◽

Herpes Simplex Virus 1 ◽

Double Stranded Rna ◽

Polycytidylic Acid ◽

Interferon Regulatory Factor 1 ◽

Mouse Macrophages ◽

Simplex Virus

Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea–induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections. HCFC2 promoted the binding of IRF1 and IRF2 to the Tlr3 promoter, without which inflammatory cytokine and type I IFN responses to the double-stranded RNA analogue poly(I:C) are reduced in mouse macrophages. HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases.

Download Full-text

Engineering species-like barriers to sexual reproduction

10.1101/079095 ◽

2016 ◽

Author(s):

Maciej Maselko ◽

Stephen C. Heinsch ◽

Jeremy Chacón ◽

William Harcombe ◽

Michael J. Smanski

Keyword(s):

Gene Expression ◽

Sexual Reproduction ◽

Model Organism ◽

Lethal Gene ◽

Proof Of Concept ◽

Wild Type ◽

Genetic Barrier ◽

Over Expression ◽

Novel Approach ◽

Engineered Strain

We introduce a novel approach to engineer a genetic barrier to sexual reproduction between otherwise compatible populations. Programmable transcription factors drive lethal gene expression in hybrid offspring following undesired mating events. As a proof of concept, we target the ACT1 promoter of the model organism Saccharomyces cerevisiae using a dCas9-based transcriptional activator. Lethal over-expression of actin results from mating this engineered strain with a strain containing the wild-type ACT1 promoter.

Download Full-text

PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities

Pathogens ◽

10.3390/pathogens9050376 ◽

2020 ◽

Vol 9 (5) ◽

pp. 376 ◽

Cited By ~ 1

Author(s):

Challika Kaewborisuth ◽

Surapong Koonpaew ◽

Kanjana Srisutthisamphan ◽

Ratchanont Viriyakitkosol ◽

Peera Jaru-ampornpan ◽

...

Keyword(s):

Type I Interferon ◽

Cellular Proteins ◽

Poly I:C ◽

Type I ◽

Type I Ifn ◽

Reading Frame ◽

Diarrhea Virus ◽

Host Interaction ◽

Iκb Kinase ◽

Porcine Epidemic Diarrhea

The Open Reading Frame 3 (ORF3), an accessory protein of porcine epidemic diarrhea virus (PEDV), has been shown to interact with a myriad of cellular proteins, among which include the IκB kinase β (IKBKB). Here, specific IKBKB domains responsible for ORF3–IKBKB interaction were identified. Dysregulation of NF-κB and Type I interferon (IFN) in the presence of ORF3 was also demonstrated. We showed that while ORF3 was capable of up-regulating IKBKB-meditated NF-κB promoter activity, it surprisingly down-regulated the activation of IKBKB-meditated IFN-β promoter and expression of IFN-β mRNA. When overexpressed, ORF3 could suppress Poly I:C mediated type I IFN production and induction. Finally, we demonstrated that IKBKB- and RIG-I-mediated type I IFN induction by ORF3 resulted in different outcomes. Our study is the first to demonstrate the potential and complex roles of ORF3 in the involvement of aberrant immune signaling as well as in the virus–host interaction.

Download Full-text

The Mll-AF9 Knock-In Fusion Gene Results in Reprogramming and Enhanced Self-Renewal of Hematopoietic Progenitors, Especially in the HSC and CLP Populations.

Blood ◽

10.1182/blood.v108.11.1421.1421 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1421-1421

Author(s):

Weili Chen ◽

Ashish R. Kumar ◽

Wendy A. Hudson ◽

Quanzhi Li ◽

John H. Kersey

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Fusion Gene ◽

Type I ◽

Myeloproliferative Disease ◽

Wild Type ◽

Self Renewal ◽

Gm Csf ◽

Young Mice ◽

In Cells

Abstract The relative importance of the major hematopoietic progenitor/stem cell populations in MLL fusion gene leukemias remains largely undefined. Several studies have demonstrated that retrovirally transformed populations will produce leukemia in mice. However, because the levels of gene expression are known to alter cellular effects and MLL fusion gene expression in previous studies is generally supraphysiologic, uncontrolled and variable, comparison of individual population is difficult. In this study, we used knock-in mice with the fusion gene inserted in the genomic DNA by homologous recombination as an alternative model, permitting study of cells in which the fusion gene is under the control of the endogenous promoter and thus expressed at physiological levels in all progenitor/stem cells. Such knock-in cells also have the advantage that there is haploinsufficiency of the Mll gene expression which may be important in cellular dysfunction. Mll-AF9 knock-in mice develop myeloproliferation as early as 6 days of age and develop myeloproliferative disease-like (MPD-like) myeloid leukemia after six months latency. We postulated that Mll-AF9 induced deregulation would result in progenitor cells with quantifiably different biologic properties. In this study, we evaluated marrow progenitor/stem cells from young mice before leukemia development. Wild type or Mll-AF9 marrow cells from 3–6 young mice (8 weeks old) were sorted into HSC, CLP, CMP and GMP populations using standard protocols and grown in methylcellulose medium containing IL-3, IL-6, SCF, and GM-CSF. After 7 days’ culture, 3.6 fold more myeloid colonies were found in GMP and 2.5 fold more in CMP groups from Mll-AF9 compared to WT mice. After the third plating generation (21 days in culture), a very different pattern emerged. As expected, only rare colonies were found from WT mice whereas Mll-AF9 HSC and CLP groups resulted in significantly more myeloid colonies (60.1±5.5 and 67.5±10.5, respectively) than the CMP and GMP groups (27.2±3.8 and 20.9±4.1, respectively). Dense compact (Type I) colonies composed of immature myeloid cell were frequent in the Mll-AF9 HSC and CLP groups. Two-dimensional Sca-1 and c-kit plots showed that Mll-AF9 resulted in increases from a mean of 6.4% to 12.9% in HSCs and 12.4 to 27.3% in CLPs. Remarkably, Mll-AF9 CLP day 7 cultures had notably high number of CD11b+Gr1+ cells (mean of 57%). Mll-AF9 CLPs cultured under myeloid conditions also showed mixed lineage characteristics: expression of myeloid genes (GM-CSF receptor, c-fms, and lysozyme) and early B lymphoid genes (IL-7 receptor, TdT but not PAX5) and D-J rearrangement. In summary, our results show that Mll-AF9, when expressed at physiologic levels, reprograms progenitor/stem cells from young mice months before development of leukemia. CLPs are remarkable because in contrast to lymphoid restricted wild type CLPs, Mll-AF9 CLPs are mixed lineage in phenotype. Mll-AF9 resulted in increased self-renewal in all four HSC, CLP, CMP, and GMP populations compared with WT populations. However, importantly, in Mll-AF9 mice, self-renewal was most enhanced in cells with more intrinsic self-renewal potential and/or more evidence of reprogramming (HSCs, CLPs) than in committed myeloid progenitors. A predicted consequence of these differences is that cells with the highest Mll-AF9 induced self-renewal (HSCs, CLPs) will be more efficient than transformed CMPs and GMPs in inducing leukemia.

Download Full-text

HDAC8 Regulates Long-Term Hematopoietic Stem Cell Quiescence and Maintenance

Blood ◽

10.1182/blood.v128.22.1468.1468 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1468-1468

Author(s):

Wei-Kai Hua ◽

Jing Qi ◽

Qi Cai ◽

Emily Carnahan ◽

Ling Li ◽

...

Keyword(s):

Cell Cycle ◽

Bone Marrow ◽

Poly I:C ◽

Control Group ◽

Wild Type ◽

Hematopoietic Stem ◽

Cell Fate Decisions ◽

Polycytidylic Acid ◽

Deficient Mice

Abstract Long-term (LT) hematopoietic stem cells (HSC) are responsible for life-long production of mature blood cells of all lineages through tightly concerted cell fate decisions including quiescence, self-renewal, differentiation and apoptosis. Histone deacetylase 8 (HDAC8) is a member of class I HDAC enzymes that remove acetyl moieties from lysine residues on histones and a variety of non-histone proteins. Specifically, HDAC8 has been shown to modulate the acetylation cycle of cohesin complex protein SMC3. Loss-of-function mutations in HDAC8, located on the X chromosome q13, have been found in patients with Cornelia de Lange Syndrome (CdLS) and those with CdLS-like features. These HDAC8 mutations are associated with severely skewed X-inactivation (100% wild type allele) in the peripheral blood of female patients, possibly due to selection against the mutant alleles. However, the expression and function of HDAC8 in normal HSCs and hematopoiesis remain unknown. In this study, we show that Hdac8 is highly expressed in the phenotypic LT-HSC (Lin-cKit+Sca1+CD150+CD48-) population in adult mice. To determine the function of HDAC8 in adult hematopoiesis, we generated conditional Hdac8 deficient mice using the Mx1-Cre and a floxed Hdac8 allele (Mx1-Cre/Hdac8f/f(y)) andconfirmed that Hdac8 is successfully deleted by polyinosinic-polycytidylic acid [poly (I:C)] treatment. Phenotypic analysis of Hdac8 deficient mice showed increased LT-HSC population compared to similarly treated control mice. However, largely normal steady state hematopoietic profile was found in Hdac8 deficient mice at 6 weeks and 1 year after induction. To further track Hdac8-deleted cells, we generated Cre/Hdac8f/f(y) mice with a dual fluorescence Rosa26mT/mG (mT/mG) Cre reporter allele, which expresses dTomato prior to Cre induction and becomes GFP+ after Cre-mediated recombination. We assessed hematopoietic repopulation by transplanting bone marrow cells from Cre/Hdac8f/f(y)/mTmG+mice (2 x 105) together with wild type support cells (2 x 105) into lethally irradiated CD45.1+ congenic recipients. Hdac8 deletion was induced by treating the recipients with 7 does (14 m▢g/kg/dose) of poly (I:C). We found that Hdac8 deletion did not affect CD45.2+ or GFP+ donor-derived overall engraftment or lineage repopulation up to 16 weeks. There was also no change in the frequency or number of GFP+ donor-derived phenotypic LT-HSCs in the bone marrow. Serial transplantation was performed to further assess long-term repopulating activity of HSCs. Hdac8 deficient cells were significantly (p=0.019; n=3) compromised in multi-lineage repopulation in secondary transplant recipients. Except a modest reduction in Pre-GM, there was no change in the overall composition of Hdac8 deficient CD45.2+-derived populations. Upon tertiary transplantation, no donor engraftment was observed for Hdac8 deficient cells (0 out of 4) compared to 50% positive engraftment in control group (4 out of 8). These results indicate that HDAC8 is crucial for maintaining long-term serial-repopulating activity over time. Cell cycle analysis revealed that Hdac8 deficient LT-HSCs display reduced quiescence and increased cycling, consistent with the increased number of phenotypic LT-HSC seen in Hdac8 deleted mice. Therefore, we further tested the sensitivity of Hdac8 deficient mice to serial ablation with 5-fluorouracil (5FU), an S phase-specific cytotoxic chemotherapeutic agent. Impaired hematopoietic recovery and increased lethality (p<0.001; n=23) was seen in Hdac8 deficient mice treated with 5-FU (100 mg/kg) every 7 days, indicating that Hdac8 deletion renders hypersensitivity to serial ablation. There were significnatly less phenotypic LT-HSCs in Hdac8 deficient mice 6 days after 5-FU treatment (p<0.01; n=4). In parallel, we observed increased DNA strand beaks as indicated by γ-H2AX staining and comet assays (p<0.001; n>100 cells). Analysis of p53 activation, cell cycle regulators and DNA dmage response are ongoing. Collectively, our study indicates that HDAC8 plays a pivotal role in LT-HSC quiescence and maintenance. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Toll-Like Receptor-3 Ligation-Induced Indoleamine 2, 3-Dioxygenase Expression in Human Trophoblasts

Endocrinology ◽

10.1210/en.2011-0278 ◽

2011 ◽

Vol 152 (12) ◽

pp. 4984-4992 ◽

Cited By ~ 19

Author(s):

Bo Wang ◽

Kaori Koga ◽

Yutaka Osuga ◽

Ingrid Cardenas ◽

Gentaro Izumi ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Conditioned Media ◽

Poly I:C ◽

Type I ◽

Toll Like Receptor ◽

Human Trophoblast ◽

Double Stranded Rna ◽

Indoleamine 2 ◽

Polycytidylic Acid

Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades an essential amino acid, tryptophan, and plays a role in inhibiting the proliferation of T cells and intracellular pathogens. Inhibiting IDO in mice leads to fetal rejection, suggesting its significance in establishing pregnancy. Toll-like receptor 3 (TLR-3) is a key component of the innate immune system that recognizes viral double-stranded RNA and triggers immune reactions by producing type I interferon. Using a human trophoblast cell culture system, we studied the effect of TLR-3 ligation on IDO expression and function by treating trophoblasts with polyinosinic-polycytidylic acid [poly(I:C)] (a synthetic double stranded RNA, which mimics viral RNA). Real-time PCR and Western blot analysis revealed that IDO mRNA and protein expression was significantly induced by poly(I:C). The activity of IDO was also increased by poly(I:C) given that the l-kynurenine concentrations were elevated in conditioned media. Conditioned media from poly(I:C)-treated trophoblasts were found to inhibit the proliferation of human T cells significantly. Poly(I:C) was also shown to induce interferon (IFN)-β mRNA expression in trophoblasts. Recombinant human IFN-β increased IDO mRNA expression in trophoblasts more rapidly than poly(I:C). Pretreating with neutralizing antibody against IFN-β significantly suppressed IDO induction by poly(I:C). Collectively we have demonstrated that ligation of TLR-3 by poly(I:C) induces IDO expression in human first-trimester trophoblasts via an IFN-β-dependent pathway. These findings suggest that upon viral infection, trophoblasts induce IDO and in turn contribute to antimicrobial activity and maintenance of fetomaternal tolerance.

Download Full-text

Suppression of Iodide Uptake and Thyroid Hormone Synthesis with Stimulation of the Type I Interferon System by Double-Stranded Ribonucleic Acid in Cultured Human Thyroid Follicles

Endocrinology ◽

10.1210/en.2006-1638 ◽

2007 ◽

Vol 148 (7) ◽

pp. 3226-3235 ◽

Cited By ~ 31

Author(s):

Kazuko Yamazaki ◽

Koichi Suzuki ◽

Emiko Yamada ◽

Tetsu Yamada ◽

Fumihiko Takeshita ◽

...

Keyword(s):

Thyroid Function ◽

Culture Medium ◽

De Novo ◽

Type I Interferons ◽

Poly I:C ◽

Human Thyroid ◽

Type I ◽

Iodide Uptake ◽

Hormone Synthesis ◽

Polycytidylic Acid

Although viral infection is thought to be associated with subacute thyroiditis and probably with autoimmune thyroid disease, possible changes in thyroid function during the prodromal period of infection or subclinical infection remain largely unknown. Recently, it was shown that pathogen-associated molecular patterns stimulate Toll-like receptors (TLR) and activate innate immune responses by producing type I interferons (IFN). Using a human thyroid follicle culture system, in which de novo synthesized thyroid hormones are released into the culture medium under physiological concentrations of human TSH, we studied the effects of polyinosinic-polycytidylic acid [Poly(I:C)], a chemical analog of viral double-stranded RNA (dsRNA), on TSH-induced thyroid function. Thyrocytes expressed ligands for dsRNA (TLR 3, CD14, and retinoic-acid-inducible protein-1) comparable with the TSH receptor. DNA microarray and real-time PCR analyses revealed that dsRNA increased the expression of mRNA for TLR3, IFN-β, IFN-regulating factors, proinflammatory cytokines, and class I major histocompatibility complex (MHC), whereas genes associated with thyroid hormonogenesis (sodium/iodide symporter, peroxidase, deiodinases) were suppressed. In accordance to these data, Poly(I:C) suppressed TSH-induced 125I uptake and hormone synthesis dose dependently, accompanied by a decrease in the ratio of 125I-T3/125I-T4 released into the culture medium, whereas peptidoglycan, lipopolysaccharides, or unmethylated CpG DNA, ligands for TLR2, TLR4, and TLR9, respectively, had no significant effect. These inhibitory effects of Poly(I:C) were not blocked by a neutralizing antibody against TLR3 and an anti-IFN α/β receptor antibody. These in vitro findings suggest that when thyrocytes are infected with certain viruses, dsRNA formed intracellularly in thyrocytes may be a cause for thyroid dysfunction, leading to development of autoimmune thyroiditis.

Download Full-text