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Primary retroperitoneal tumours
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Isaac R Francis, Richard H Cohan, William R Burns
Solitary fibrous tumours (SFTs) are rare spindle cell neoplasms. These were previously classified as hemangiopericytomas and/or giant cell angiofibromas. These tumours are CD34 positive and overexpress the STAT6 protein. The majority of these tumours are benign, but up to 20% may demonstrate aggressive malignant behaviour. While SFTs most commonly arise from the pleura, the most common extrapleural site is the retroperitoneum (2,6,7). Fewer than 5% of patients may present with hypoglycaemia—Doege–Potter syndrome (41).
Local mucosal allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Ibon Eguiluz-Gracia, Paloma Campo, Carmen Rondón
Similar to the other isotypes, the generation of high-affinity sIgE requires the activation of the adaptive immune system. Class switch recombination to IgE (εCSR) in GC B cells has a stronger dependence on Tfh cell collaboration than the other isotypes [18]. The initiation of εCSR requires the interaction of CD40L expressed on GC B cells with CD40 induced on activated type 2 Tfh cells, which also provide IL-4, the crucial inductor for the process [19]. Additional initiators of εCSR include the stimulation of a proliferation-inducing ligand (APRIL) and toll-like receptor-4 (TLR4) on GC B cells by B-cell activating factor (BAFF) and LPS, respectively [20]. Globally, these stimuli activate the transcription factor STAT6, which induces the gene changes resulting in εCSR [19]. The differences between IgE and other immunoglobulin isotypes are even more pronounced for the affinity maturation process after CSR [21]. Switched IgE+ B cells cannot efficiently traffic to the light zone of the GCs in order to undergo their positive selection after somatic hypermutation [20]. The increased residence of IgE+ B cells in the GC dark zone results in increased apoptosis of IgE+ B cells and impaired formation of IgE+ memory B cells (Figure 9.1). These factors result in a reduced number of IgE+ memory B cells and inefficient affinity maturation of GC-derived IgE antibodies [22].
The respiratory system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
This is a rare tumour of submesothelial fibroblasts. It is often asymptomatic but some patients have cough, dyspnoea, finger clubbing, and hypoglycaemia. They are greyish/white, nodular, or lobulated tumours often attached to the lung by a pedicle. They are composed of spindle cells and harbour a characteristic NAB2-STAT6 fusion gene which leads to the overexpression of STAT6 which can aid in diagnosis. They are usually benign but some tumours can behave in a more aggressive fashion, invading the underlying lung. However, both are generally cured by complete surgical excision.
House dust mite-induced endoplasmic reticulum stress mediates MUC5AC hypersecretion via TBK1 in airway epithelium
Published in Experimental Lung Research, 2023
Jun Deng, Hongmei Tang, Yun Zhang, Xiefang Yuan, Ning Ma, Hang Hu, Xiaoyun Wang, Chunfeng Liu, Guofeng Xu, Yuejiao Li, Songping Wang, Linlin Guo, Xing Wang
Previously, we found that NF-κB mediates IL-13 to regulate the overproduction of MUC5AC.15 ER stress upregulates the expression of the inflammation response factor, NF-κB.16 A role for NF-κB has been demonstrated in the pathogenesis of ovalbumin (OVA)-induced airway inflammation in mice, as described by Helal et al.17 Fujisawa et al. reported that activated NF-κB binds to the MUC5AC promoter region to induce gene expression.18 Foster et al. noted that STAT6 is involved in the pathogenesis of experimental chronic asthma, and studies have shown that the human STAT6 gene is important for the pathogenesis of asthmatic and allergic disease.19,20 Additionally, STAT6-deficient mice do not develop airway hyper-responsiveness when challenged with OVA.21,22
Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid
Published in Annals of Medicine, 2023
Fangyuan Chen, Yiman Wang, Xinyi Chen, Nan Yang, Li Li
IL-4 can bind to two receptors, the type I receptor and type II receptor. Type I receptors are mainly distributed on lymphocytes and myeloid cells, whereas type II receptors are present on myeloid cells and all non-hematopoietic cells (Figure 1) [70]. Type I receptors are composed of IL-4Rα and γc, whereas type II receptors are composed of IL-4Rα and IL-13Rα1 [71]. IL-13Rα1 not only serves as a subunit of type II receptors for binding IL-4 but also a receptor for IL-13 (Figure 1). Once IL-4 binds with type I receptors or type II receptors, downstream signaling molecules, such as Janus kinase (JAK) 3, JAK1, or JAK2/tyrosine kinase 2 (TYK2) are activated [71]. These signaling molecules then phosphorylate with each other to induce changes in the cytoplasmic tails of receptors, which serve as docking sites for downstream signaling molecules like signal transducer and activator of transcription 6 (STAT) and insulin receptor substrate (IRS) [71]. STAT6 and IRS are the two main pathways in IL-4/13 signaling. STAT6 can bind with DNA sequences to initiate gene transcription, while the IRS-2 pathway does not translocate to the nucleus but activate signaling molecules like PI3-K [72,73] to initiate gene transcription. The STAT6 pathway has been well-studied in asthma, where it is responsible for Th2 differentiation and eosinophil migration. However, the IRS pathway is presumed to be critical for cancer proliferation and metastasis [71].
Long Non Coding RNA FOXD3‑AS1 Alleviates Allergic Rhinitis by Elevating the Th1/Th2 Ratio via the Regulation of Dendritic Cells
Published in Immunological Investigations, 2023
Hao Zhang, Xinhua Zhu, Hongbing Liu, Chunping Yang, Yuehui Liu
STATs are closely associated with T-cell differentiation. IL-4 and IL-13 can activate STAT6, and activated STAT6 induces the secretion of Th2 cytokines, thus resulting in the occurrence of Th2 inflammation (Thomas et al. 2016). Liang et al. (2019) reported that Morin ameliorated ovalbumin-induced AR via inhibition of the STAT6 and GATA3/T-bet signaling pathways in BALB/c mice. In addition, cisplatin and oxaliplatin inhibited the phosphorylation of STAT6 during the differentiation and maturation of DCs (de Haas et al. 2019). Thus, we speculated that LV-FOXD3-AS1 may affect DC maturation by regulating the phosphorylation of STAT6 in AR. As expected, our data revealed that LV-FOXD3-AS1 markedly inhibited the phosphorylation of STAT6 in DCs, and overexpressing STAT6 effectively reversed the decrease in the percentages of CD80-, CD86-, and MHC-II-positive DCs induced by LV-FOXD3-AS1. Regrettably, we only examined the change in STAT6. It will be better to clarify whether STAT6 is the major transcription factor involved in the regulation of DC maturation in AR by assessing other STATs.