Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model

Ueki, Ikuko; Abiru, Norio; Kawagoe, Kentaro; Nagayama, Yuji

doi:10.1530/joe-11-0129

Cited by 9 publications

(5 citation statements)

References 28 publications

(46 reference statements)

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“…In addition, TNF-α, IL-6, IL-8 IL-10 and IL-13 have already been described for various involvements in TAO. These include (i) stimulation of the glycosaminoglycan production in vitro in ocular fibroblast for TNF-α 30 , 31 , (ii) secretion by orbital fibroblasts under the stimulation of TSHR antibodies or prostaglandin E2 for IL-6 32 – 34 , (iii) expression by fibrocytes that can induce the infiltration of inflammatory cells and subsequent tissue remodelling for IL-8 35 and the steroid treatment which decreases its expression level for IL-8 22 and (iv) regulation of both T and B-cells functions for IL-10 36 . Finally, for all of them, genetic polymorphism of their gene in relation with TAO have been identified in different populations 21 , 37 – 44 .…”

Section: Discussionmentioning

confidence: 99%

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Kishazi

Dor

Eperon

et al. 2018

Sci Rep

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The aim was to investigate the levels of cytokines and soluble IL-6R in the tears of patients with thyroid-associated orbitopathy (TAO) disease. Schirmer’s test was adopted to collect tears from TAO patients (N = 20, 17 women, mean age (±SD): 46.0 years (±13.4)) and healthy subjects (N = 18, 10 women, 45.4 years (±18.7)). Lacrimal cytokines and soluble IL-6R (sIL-6R) were measured using a 10-plex panel (Meso Scale Discovery Company) and Invitrogen Human sIL-6R Elisa kit, respectively. Tear levels of IL-10, IL-12p70, IL-13, IL-6 and TNF-α appeared significantly higher in TAO patients than in healthy subjects. Interestingly, IL-10, IL-12p70 and IL-8 levels increased in tears whatever the form of TAO whereas IL-13, IL-6 and TNF-α levels were significantly elevated in inflammatory TAO patients, meaning with a clinical score activity (CAS) ≥ 3, compared to controls. Furthermore, only 3 cytokines were strongly positively correlated with CAS (IL-13 Spearman coeff. r: 0.703, p = 0.0005; IL-6 r: 0.553, p = 0.011; IL-8 r: 0.618, p = 0.004, respectively). Finally, tobacco use disturbed the levels of several cytokines, especially in patient suffering of TAO. The differential profile of lacrimal cytokines could be useful for the diagnosis of TAO patients. Nevertheless, the tobacco use of these patients should be taken into account in the interpretation of the cytokine levels.

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Section: Discussionmentioning

confidence: 99%

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Kishazi

Dor

Eperon

et al. 2018

Sci Rep

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“…For instance, it inhibits the activities of nuclear factor-κB and alters the JAK-STAT signaling pathway ( 16 ). A previous study on a murine model indicated that IL-10 deficiency reduces the induction of anti-thyroid stimulating hormone receptor antibodies; thus, IL-10 plays an important role in the development of GD in mice ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Expression levels and genetic polymorphisms of interleukin-2 and interleukin-10 as biomarkers of Graves’ disease

Liang

Wen

Dong

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to determine whether the expression levels of interleukin (IL)-2 and IL-10 may be used as biological markers in Graves’ disease (GD) patients. A total of 256 individuals, including 118 GD patients and 138 healthy individuals, were enrolled into the study. Blood samples were collected from each patient and healthy individual, which were then subjected to enzyme-linked immunosorbent assay (ELISA). Total RNA and total proteins were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. In addition, restriction fragment length polymorphism (RFLP) analysis was performed to detect the presence of genetic polymorphisms. The ELISA results indicated that the IL-2 and IL-10 serum levels in the GD patients were increased by ~5.2 and ~7-fold when compared with the levels in the healthy controls. The results of RT-qPCR indicated that the mRNA expression levels of IL-2 and IL-10 were upregulated in the GD patients when compared with the healthy controls. Furthermore, the western blot analysis results revealed that the protein expression levels of IL-2 and IL-10 were significantly increased in the GD patients. RFLP analysis indicated that the increased number of GG single nucleotide polymorphisms (SNPs) in the GD group were detected in the −330 locus of the IL-2 promoter and the −1082 locus of the IL-10 promoter. In addition, the results indicated that the relatively high rates of homozygous GG SNPs (IL-2 −330T/G and IL-10 −1082A/G polymorphisms) on the alleles may be associated with the incidence of GD. The serum, mRNA and protein expression levels of IL-2 and IL-10 were significantly increased in GD patients when compared with the levels in the healthy controls. In conclusion, the expression levels and genetic polymorphisms of IL-2 and IL-10 may be potential biomarkers for the incidence of Graves’ disease in the population studied.

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“…That is the main reason why the two autoimmune thyroiditis have different clinical pictures. It is decided by the characteristics of autoantibodies [82]. Like SLE, anti-nuclear antibodies can be detected in autoimmune thyroiditis, especially in Grave's disease.…”

Section: Thαβ Immunological Pathway Related With Grave's Diseasementioning

confidence: 99%

<strong></strong>Type 2 Hypersensitivity Disorders including Systemic Lupus Erythematosus, Sjogren’s Syndrome, Grave’s Disease, Myasthenia Gravis, Immune Thrombocytopenia, Autoimmune Hemolytic Anemia, Dermatomyositis, and Graft versus Host Disease Are THab Dominant A

2024

Preprint

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Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.

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Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model

Cited by 9 publications

References 28 publications

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Expression levels and genetic polymorphisms of interleukin-2 and interleukin-10 as biomarkers of Graves’ disease

<strong></strong>Type 2 Hypersensitivity Disorders including Systemic Lupus Erythematosus, Sjogren’s Syndrome, Grave’s Disease, Myasthenia Gravis, Immune Thrombocytopenia, Autoimmune Hemolytic Anemia, Dermatomyositis, and Graft versus Host Disease Are THab Dominant A

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