Increased Expression of Thymic Stromal Lymphopoietin and Its Receptor in Kimura's Disease

Abstract

Objective: The objective of this study was to investigate the expression of thymic stromal lymphopoietin (TSLP) and TSLP receptor (TSLPR) in Kimura's disease (KD). Methods: Using parotid gland tissues from KD patients and control subjects, we quantified the expression levels of mRNA for TSLP, interleukin (IL)-25, IL-33, and their receptors by massively parallel sequencing. We also performed immunohistochemical analysis of TSLP and TSLPR, and counted cells immunoreactive for these proteins by the polymer immunocomplex and double immunofluorescence methods. Results: The levels of mRNA for TSLP, TSLPR, and IL-25R, but not IL-25, IL-33, or IL-33R, were significantly elevated in parotid gland tissues from the KD group as compared to the control group. Immunohistochemical analysis revealed that TSLP- and TSLPR-positive cells were significantly increased in number in parotid gland tissues from KD patients. Double immunofluorescence staining showed that TSLP and TSLPR were localized mainly in CD68-positive macrophages and tryptase-positive mast cells, respectively. Conclusions: Overexpression of TSLP and TSLPR might contribute to the pathogenesis of KD through interactions between macrophages and mast cells. Regulation of TSLP/TSLPR signaling may be a potential therapeutic approach for KD.

Expression of the interleukin-21 and phosphorylated extracellular signal regulated kinase 1/2 in Kimura disease

“…Elevation of IL-4, IL-5, IL-6, IL-10, IL-13, IL-22, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSL), TSL receptor, IL-25 receptor, eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), CC-chemokine receptor 3 (CCR3), tumour necrosis factor-α, eosinophil cationic protein, major basic protein, sIL-2 receptor, thymus and activation regulated chemokine (TARC/CCL17), eotaxin-3/CCL26, vascular endothelial growth factor and prostaglandin D2, 25 27–41 and reduction of IL-17 27 were seen in KD, whereas IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IL-25, IL-33, IL-33 receptor, interferon-γ, GM-CSF 27 29 30 33 35 37 42 were within the normal ranges. Although there were several inconsistencies, an overwhelming majority of researchers, in our opinion, agree that Th2 polarisation and the increased syntheses of Th2-type cytokines may play crucial roles in the pathogenesis of Kimura disease.…”

Basophils are increased and express increased levels of interleukin-4 in the parotid lesions of Kimura disease

“…[ 19 ]. In KD, TSLP is the only one of these 3 cytokines that is increased in the lesional sites, and it is thought to play an important role in induction of Th2 inflammation in KD [ 9 ]. Furthermore, it was found that, in KD, macrophages between the lymphoid follicles produce mainly TSLP, while mast cells express the TSLP receptor [ 9 ].…”

“…The subjects and tissue specimens were the same as those reported and employed in our earlier study [ 9 ]. Briefly, we obtained parotid gland tissue specimens from 6 male patients with KD (mean age ± standard error of the mean, 34.5 ± 6.9 years).…”

“…Histopathological analyses were performed as described in our earlier manuscript [ 9 ]. Briefly, haematoxylin and eosin staining was performed to confirm the diagnosis of KD, while Congo red staining was used to determine the eosinophil counts in the KD and normal parotid glands.…”

“…The detailed methods were as described in our earlier manuscript [ 9 ]. Briefly, 3-m sections were cut from paraffin-embedded tissue blocks were deparaffinized, rinsed in ethanol, rehydrated, and rinsed in phosphate-buffered saline (PBS; pH, 7.6).…”