Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2h4 mice

Shi, Liwei; Bi, Mei; Yang, Rong; Zhou, Jin; Zhao, Shimeng; Fan, Chenling; Shan, Zhongyan; Li, Y.; Wang, Teng

doi:10.1007/s40618-013-0013-1

Cited by 20 publications

(16 citation statements)

References 24 publications

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“…This may be explained by the fact that Tg is the only self-antigen that undergoes post-translational modification as a consequence of the environmental supply of iodine, with the exposure of previously hidden epitopes . In experimental animals, enhanced iodination of Tg facilitates processing and presentation of a cryptic pathogenic peptide [22,23,24,25]. In agreement with this concept is the observation that iodine may play a role in central tolerance, and T cells undergoing thymic selection likely recognize only noniodinated Tg epitopes [21].…”

Section: Iodine and Thyroid Diseasementioning

confidence: 98%

Iodine, Thyroid Autoimmunity and Cancer

2015

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This review focuses on two different topics: (a) iodine and autoimmune thyroid disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake modifies the expression of thyroid diseases and has been associated with induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated Tg, as suggested in animal models. We have shown that the unmasking of a cryptic epitope on Tg contributes to iodine-induced thyroid autoimmunity in humans. The relationship between AITD and PTC has been suggested in many studies. The presence of two different mechanisms has been hypothesized, one typical of AITD and the other of an immune reaction to PTC. We have shown that in AITD, the pattern of Tg recognition by anti-Tg antibodies (TgAb) is ‘restricted' to the immunodominant regions of Tg, while in patients with non-AITD, such as nodular goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid function may also affect the frequency of PTC, the risk of cancer increasing with serum TSH levels. We have shown that this mechanism, rather than thyroiditis per se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as a consequence of the autoimmune process leading to a progressive increase of serum TSH in these patients.

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Section: Iodine and Thyroid Diseasementioning

confidence: 98%

Iodine, Thyroid Autoimmunity and Cancer

2015

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“…The IL-10 increase is also demonstrated during treatment with anti-inflammatory agents like ellagic acid or meloxicam, while B cell-induced IL-10 secretion by Tregs or DCs is associated with recovery of Kawasaki Disease (KD), nonobese diabetes, MS, autoimmune thyroiditis (AT), etc. [110][111][112][113][114]. With respect to systemic lupus erythematous (SLE), both the percentage of circulating Breg cells and the ability to produce IL-10 were elevated; the percentage of Breg cells increased during SLE flares and decreased following disease remission [115].…”

Section: Principal Immune Conditionsmentioning

confidence: 99%

“…Björkbacka et al have proposed that, during early stages of atherosclerosis, Tregs and anti-inflammatory cytokine IL-10 can control autoimmune response against plaque antigens due to inhibition of the activity of autoreactive Th1 effector T cells [117]. Meanwhile, mice with AT and inflammatory bowel disease had a decreased CD1d(hi)CD5CD19 Breg subset and reduced IL-10 mRNA expression in splenocytes and maintained relatively low IL-10 levels during the development of thyroiditis or colitis [108,114]. Taken together, these findings indicate that the defective expression of Breg cells combined with impaired Tregs and enhanced Th17 cells plays an important role in the development of autoimmune pathologies [104,108,114].…”

Section: Principal Immune Conditionsmentioning

confidence: 99%

“…Meanwhile, mice with AT and inflammatory bowel disease had a decreased CD1d(hi)CD5CD19 Breg subset and reduced IL-10 mRNA expression in splenocytes and maintained relatively low IL-10 levels during the development of thyroiditis or colitis [108,114]. Taken together, these findings indicate that the defective expression of Breg cells combined with impaired Tregs and enhanced Th17 cells plays an important role in the development of autoimmune pathologies [104,108,114]. The IL-10 production is associated both with protective and pathogenic responses, while experimental data from animal studies indicate that modulation of mentioned immune responses represents a promising new target for treatment of autoimmune diseases [117].…”

Section: Principal Immune Conditionsmentioning

confidence: 99%

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Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

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The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

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“…In fact, iodine feeding decreases the proportion of CD4 + CD25 + Foxp3 + T regs in the spleen (12,13) and thyroid glands (14) of NOD-H2 h4 mice. In addition, NOD-H2 h4 mice lacking the T cell costimulatory molecule CD28 develop a more severe form of iodine-accelerated thyroiditis and have fewer T regs in spleen and cervical lymph nodes (15).…”

Section: Introductionmentioning

confidence: 95%

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

Sharma

Dalmazi

Caturegli

2016

Thyroid

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Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2 h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. Conclusions: This study shows that CTLA-4 blockade exacerbates the iodine-accelerated form of thyroiditis typical of the NOD-H2 h4 mouse. The study could also have implications for cancer patients who develop thyroiditis as an immune-related adverse event after CTLA-4 blockade.

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Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2h4 mice

Abstract: The defective expression of Breg cells combined with impaired Treg cells and enhanced Th17 cells might play an important role in the development of iodine-induced AIT in NOD.H-2(h4) mice.

Cited by 20 publications

References 24 publications

Iodine, Thyroid Autoimmunity and Cancer

Iodine, Thyroid Autoimmunity and Cancer

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

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