Relationship between Disease Duration and Predominant Orbital T Cell Subset in Graves’ Ophthalmopathy

Aniszewski, Jaroslaw P.; Valyasevi, Rosanee W.; Bahn, Rebecca S.

doi:10.1210/jcem.85.2.6333

Cited by 65 publications

(48 citation statements)

References 29 publications

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“…On the other hand, the finding that CXCL10 production declines at level of both thyroid gland and serum in GD, but not in HT patients in the later phases of these disorders, may be consistent with the results of another study suggesting a progressive switch from Th1-to Th2-polarized profile in the course of GD but not in HT [85]. This shift probably reflects a counter regulatory mechanism against inflammation, which has been observed even in other diseases [86,87].…”

Section: Cxcr3-binding Chemokines In Autoimmune Thyroid Disorderssupporting

confidence: 91%

CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets

Lazzeri

Romagnani²

2005

curr drug targets immune endocr metabol disord

106

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The goal to attenuate inflammation without inducing generalized immunosuppression has focused the attention on chemokines, a family of chemotactic peptides that regulate the leukocyte traffick into tissues. However, the development of drugs that block ckemokine activity may be hampered by the observation that some chemokines display pleiotropic biologic functions. For example, the chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC exhibit the ability to recruit different leukocytes subsets, the capacity to induce the proliferation of vascular pericytes as well as powerful anti-tumor effects, which are mediated by a common receptor, named CXCR3. Because of their pleiotropic biologic effects, these chemokines have been proposed as possible therapeutic targets in cancer, allograft rejection, glomerulonephritis, diabetes, multiple sclerosis, and autoimmune disorders of the thyroid. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including angiostatic effects, although its specific receptor has remained unknown for a long time. Recently, we provided evidence that the different functions of CXCL9, CXCL10, and CXCL11 on distinct cell types can be at least partly explained by the interaction of these chemokines with two distinct receptors. Indeed, in addition to the classic form of CXCR3 receptor, which we have renamed as CXCR3-A, a novel CXCR3 receptor variant (CXCR3-B) was identified, that not only mediates the angiostatic activity of CXCR3 ligands, but also acts as functional receptor for CXCL4. In this review, we focus on the accumulating evidence demonstrating the pivotal role of CXCR3-binding chemokines in several human diseases. Studies based on CXCR3 targeting have shown its importance in different pathologic conditions and orally active small molecules capable of inhibiting this receptor are now being developed in order to be tested for their activity in humans.

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Section: Cxcr3-binding Chemokines In Autoimmune Thyroid Disorderssupporting

confidence: 91%

CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets

Lazzeri

Romagnani²

2005

curr drug targets immune endocr metabol disord

106

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“…Other researchers analyzed T helper (Th) cell subsets in orbital adipose/connective tissues of GO patients, and Th1-type clone was detected predominantly in patients with recent onset (<2 yr). In contrast, Th2-type clone was overwhelming in patients with more remote onset (>2 yr) of the disease [24]. Our team found an increased number of CD4 + IL-17 + T cells and a higher expression of RORγt mRNA in GO patients, but not in GD patients.…”

Section: Discussionmentioning

confidence: 87%

Imbalance of Th17/Treg in Different Subtypes of Autoimmune Thyroid Diseases

Yuan²,

Zhu³

et al. 2016

Cell Physiol Biochem

100

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Aims: To clarify the imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases (AITDs) including Graves' disease(GD), Hashimoto's thyroiditis(HT) and Graves' ophthalmopathy (GO). Methods: 47 patients with AITD (including 16 GD, 15 HT, and 16 GO) and 12 healthy controls were enrolled in this study. The percentages of Th17 and Treg cells, the ratio of Th17/Treg, as well as their related transcription factors RORγt and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry and real-time quantitative PCR Results: Compared with those in control group, the percentage of CD4⁺IL-17⁺T cell(Th17) and the mRNA expression of its transcription factor RORγt were higher in PBMCs of AITDs (P<0.05), particularly in HT subgroup (P<0.01). The percentage of CD4⁺Foxp3⁺T (Treg) cells and its transcription factor Foxp3 mRNA were significantly decreased in PBMCs of GD (P<0.05). In addition, the ratio of Th17/Treg was elevated in AITD group and GO subgroup (P<0.01). In GO subgroup, the patients with clinical activity score (CAS) above 4.5 had higher percentages of Th17 than those with CAS ranging from 3 to 4.5 (P<0.05). Conclusion: Increased Th17 lymphocytes may play a more important role in the pathogenesis of HT and GO while decreased Treg may be greatly involved in GD.

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“…Rosi and Pio exert a dosedependent inhibition of IFN␥ and TNF␣-induced chemokines CXCL9, CXCL10, and CXCL11 secretion in orbital fibroblasts, preadipocytes, and thyrocytes (55,56). These studies indicate that PPAR␥ activity is involved in the regulation of IFN␥-induced chemokine expression in thyroid autoimmunity and TED, and PPAR␥ activators might attenuate the recruitment of activated T cells at sites of T helper type 1 (Th1)-mediated inflammation, which predominates in early stage of TED (whereas Th2 cells are more abundant later in TED) (57). Our results demonstrate that the PPAR␥ ligands Pio and Rosi inhibit TGF-␤ mediated functions including elevating HAS1 and HAS2 mRNA levels, HA production, and T cell-fibroblast adhesion.…”

Section: Discussionmentioning

confidence: 90%