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Slit2 May Underlie Divergent Induction by Thyrotropin of IL-23 and IL-12 in Human Fibrocytes.

Slit2 可能是促甲状腺素诱导人纤维细胞 IL-23 和 IL-12 的基础。

  • 影响因子:4.41
  • DOI:10.4049/jimmunol.1900434
  • 作者列表:"Fernando R","Atkins SJ","Smith TJ
  • 发表时间:2020-02-21
Abstract

:IL-23 and IL-12, two structurally related heterodimeric cytokines sharing a common subunit, divergently promote Th cell development and expansion. Both cytokines have been implicated in the pathogenesis of thyroid-associated ophthalmopathy (TAO), an autoimmune component of Graves disease. In TAO, CD34+ fibrocytes, putatively derived from bone marrow, can be identified in the orbit. There they masquerade as CD34+ orbital fibroblasts (OF) (CD34+ OF) and cohabitate with CD34- OF in a mixed fibroblast population (GD-OF). Slit2, a neural axon repellent, is expressed and released by CD34- OF and dampens the inflammatory phenotype of fibrocytes and CD34+ OF. In this study we report that thyrotropin (TSH) and the pathogenic, GD-specific monoclonal autoantibody, M22, robustly induce IL-23 in human fibrocytes; however, IL-12 expression is essentially undetectable in these cells under basal conditions or following TSH-stimulation. In contrast, IL-12 is considerably more inducible in GD-OF, cells failing to express IL-23. This divergent expression and induction of cytokines appears to result from cell type-specific regulation of both gene transcription and mRNA stabilities. It appears that the JNK pathway activity divergently attenuates IL-23p19 expression while enhancing that of IL-12p35. The shift from IL-23p19 expression in fibrocytes to that of IL-23p35 in their derivative CD34+ OF results from the actions of Slit2. Thus, Slit2 might represent a molecular determinant of balance between IL-23 and IL-12 expression, potentially governing immune responses in TAO.

摘要

: IL-23 和 IL-12,两个结构相关的异二聚体细胞因子共享一个共同的亚基,分化促进 Th 细胞发育和扩增。这两种细胞因子都与甲状腺相关眼病 (TAO) 的发病机制有关,TAO 是 Graves 病的一种自身免疫成分。在 TAO 中,推测来源于骨髓的 CD34 + 纤维细胞可以在眼眶中被识别。在那里,他们伪装成 CD34 + 眼眶成纤维细胞 (OF) (CD34 + OF),并与混合成纤维细胞群体 (GD-OF) 中的 CD34-共同生长。Slit2 是一种神经轴突驱避剂,由 CD34-OF 表达和释放,抑制纤维细胞和 CD34 + of 的炎症表型。在这项研究中,我们报道了促甲状腺激素 (TSH) 和致病性的 GD 特异性单克隆抗体 M22 在人纤维细胞中强烈诱导 IL-23; 然而, 在基础条件下或 TSH 刺激后,这些细胞中基本检测不到 IL-12 的表达。相反,IL-12 在 GD-OF 中更易诱导,细胞不能表达 IL-23。这种细胞因子的发散表达和诱导似乎是由于细胞类型特异性调控基因转录和 mRNA 稳定性的结果。似乎 JNK 通路的活性分化减弱了 IL-23p19 的表达,同时增强了 IL-12p35 的表达。从纤维细胞中的 IL-23p19 表达到其衍生物 CD34 + 中的 IL-23p35 的转变是由 slit2 的作用导致的。因此,Slit2 可能代表 IL-23 和 IL-12 表达之间平衡的分子决定因素,可能控制 TAO 中的免疫反应。

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影响因子:2.13
发表时间:2020-01-02
DOI:10.1093/ajcp/aqz145
作者列表:["Travaglino A","Pace M","Varricchio S","Insabato L","Giordano C","Picardi M","Pane F","Staibano S","Mascolo M"]

METHODS:OBJECTIVES:To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS:Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS:Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS:Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.

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影响因子:2.24
发表时间:2020-01-08
DOI:10.1007/s00268-019-05337-9
作者列表:["Lee, Inhwa","Kim, Hyeung Kyoo","Soh, Euy Young","Lee, Jeonghun"]

METHODS:Background Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. Methods Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. Results In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. Conclusions The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.

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影响因子:2.69
发表时间:2020-01-29
DOI:10.1016/j.bbrc.2019.11.047
作者列表:["Zhang Z","Xu T","Qin W","Huang B","Chen W","Li S","Li J"]

METHODS::PTPN2 is one of the members of the protein Tyrosine Phosphatases (PTPs) family. To explore the promotive effect of upregulated PTPN2 induced by inflammatory response or oxidative stress on the progression of thyroid cancer. PTPN2 level in thyroid cancer tissues and cell lines was detected. Kaplan-Meier method was applied for evaluating the prognostic value of PTPN2 in thyroid cancer patients. After stimulation of inflammatory response (treatment of IFN-γ and TNF-α), or oxidative stress (treatment of H2O2), protein level of PTPN2 in K1 cells was measured by Western blot. Regulatory effects of PTPN2 on EdU-positive staining and Ki-67 positive cell ratio in K1 cells either with H2O2 stimulation or not were determined. PTPN2 was upregulated in thyroid cancer tissues and cell lines. Its level was higher in metastatic thyroid cancer patients than those of non-metastatic ones. High level of PTPN2 predicted worse prognosis of thyroid cancer. Treatment of either IFN-γ or TNF-α upregulated protein level of PTPN2 in K1 cells. Meanwhile, H2O2 stimulation upregulated PTPN2, which was reversed by NAC administration. With the stimulation of increased doses of H2O2, EdU-positive staining and Ki-67 positive cell ratio were dose-dependently elevated. Silence of PTPN2 attenuated proliferative ability and Ki-67 expression in K1 cells either with H2O2 stimulation or not. Inflammatory response or oxidative stress induces upregulation of PTPN2, thus promoting the progression of thyroid cancer.

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