IL-9 mRNA Levels Research Articles

DUSP8 Promotes IL-9 Transcription by Inactivating Pur-α leading to asthma and atopic dermatitis

Abstract Dual-specificity phosphatase 8 (DUSP8) is a member of the DUSP family. DUSP8 dephosphorylates and inactivates the kinase JNK. DUSP8 protein levels are predominantly expressed in CD4+ T cells and platelets. DUSP8 dephosphorylates and inactivates specifically JNK in Jurkat T cells; however, the in vivo role of DUSP8 in T cells remains unclear. Using T-cell-specific DUSP8 conditional knockout (T-DUSP8 cKO, DUSP8f/f;CD4-Cre) mice, mass spectrometry, and chromatin-immunoprecipitation sequencing, we found that DUSP8 stimulated IL-9 gene expression and Th9 differentiation. TGF-β stimulated DUSP8 phosphatase activity in T cells. Mechanistically, DUSP8 dephosphorylated the transcriptional repressor Pur-α upon TGF-β signaling, leading to the nuclear export of Pur-α and subsequent IL-9 transcriptional activation. Furthermore, Il-9 mRNA levels in murine T cells were induced in Pur-α knockout. Reduction of IL-9 levels in T cells of T-DUSP8 cKO mice was reversed by Pur-α heterozygous knockout. Consistently, T-DUSP8 cKO mice displayed reduction of IL-9 and Th9-mediated immune responses in allergy, autoimmune responses, and anti-tumor immunity. Remarkably, DUSP8 overexpression and DUSP8-Pur-α interaction indeed occurred in the peripheral blood T cells of patients with asthma or atopic dermatitis, contributing to IL-9 overproduction in patients’ T cells. Thus, DUSP8 plays a critical role in the pathogenesis of asthma and atopic dermatitis, as well as autoimmune disease and cancer.

The expression of Th9 and Th22 cells in rats with cerebral palsy after hUC-MSC transplantation.

This study aimed to investigate the expression of Th9 and Th22 cells in rats with cerebral palsy (CP) after human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation. First, hUC-MSCs were isolated from fresh umbilical cords and identified. Rats were divided into the normal group, CP group, and hUC-MSC transplantation group. The Morris water maze and balance beam tests were performed to evaluate the neurobehavioral ability of the rats. The levels of TNF-α, IL-6, IL-9, and IL-22 in rat brain tissues were detected by ELISA. Th9 and Th22 proportions in brain tissues were detected by flow cytometric analysis. The mRNA levels of IL-9, IL-22, PU.1, and AHR in brain tissues were determined by qRT-PCR. hUC-MSC transplantation enhanced the neurobehavioral ability of CP rats. Furthermore, Th9 and Th22 proportions were decreased in brain tissues from CP rats after hUC-MSC transplantation. The levels of proinflammatory cytokines (TNF-α and IL-6), Th9-related IL-9 and PU.1, and Th22-related IL-22 and AHR were markedly higher in brain tissues from CP rats than in brain tissues from control rats, but their levels were significantly decreased after hUC-MSC transplantation. Our data indicate that Th9 and Th22 proportions are decreased in CP rats after hUC-MSC transplantation.

Th 9 cells in Behçet disease: Possible involvement of IL-9 in pulmonary manifestations

Behçet disease (BD) is a multisystemic disease some of whose manifestations are characterized by pulmonary involvements. The purpose of the study was to evaluate the level of T-helper type 9 (Th9) cells and the cytokine interleukin (IL)-9 in peripheral blood and in bronchoalveolar lavage (BAL) of patients with Behçet's disease (BD) affected by pulmonary manifestations. Nevertheless, until recently there have been no studies on its role in BD.The Th9 (CD4+IL-9+T) cell, transcription factor PU.1 and IL-9 mRNA levels, as well as serum and BAL IL-9 concentration, were measured in BD patients and healthy controls.The Th9 cell percentage and absolute number, PU.1 and IL-9 expression levels of BD patients were all increased significantly compared with the control group. Absolute number of Th9 cells was particularly increased in patients with active BD compared to inactive BD patients. The levels of IL-9 associated to Th9 expression depended on BD severity. These parameters were markedly expressed in the BAL of BD patients with pulmonary manifestations. IL-17 and the epithelial inflammatory cytokine TSLP were significantly correlated to IL-9 levels. This cytokine trio decreased in inactive BD patients after corticosteroïd treatment. In addition, IL-9 levels were correlated to CD4+ IL-9+ cells in BAL and in PBMCs. LPS stimulated PBMCs and macrophages induced increased secretion of IL-9 and the encoding transcription factors PU.1 and IRF4.In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of BD, which may be supported by the increased release of IL-17 and TSLP. We provide evidence that Th9 T cells are increased in BD patients with pulmonary manifestations. This suggests an important role of IL-9 in the pathogenesis of BD particularly in patients suffering from lung involvement.

The Potential Role of Th9 Cell Related Cytokine and Transcription Factors in Patients with Hepatic Alveolar Echinococcosis.

Human alveolar echinococcosis (AE) is a lethal parasitic infectious disease which may lead to liver failure if left untreated. It is caused by the larval stage of the fox tapeworm Echinococcus multilocularis and usually develops a substantial infiltrative occupation in solid organs. During the infection, T helper subsets are known to play crucial role in crosstalk between the parasite and human host. Th9 cells, a new member of CD4+ T cell family which is characterized by its specific cytokine IL-9 and transcription factors PU.1 and IRF-4, have been known recently to have a critical role in allergic diseases, and cancers as well as the parasitic infection. To assess the potential role of Th9 cells during the infection, the mRNA levels of IL-9, PU.1, and IRF-4 both in peripheral blood mononuclear cells and in liver tissues were, respectively, detected by using real-time PCR. The plasma concentration levels of IL-9 were detected by using enzyme linked immunosorbent assay (ELISA). Th9 related cytokine IL-9 and transcription factors PU.1 and IRF-4 mRNA levels elevated both in PBMCs, and in hepatic lesion and paralesion tissues in AE patients. This may facilitate the infiltrative growth of the parasite and its persistence in human host.

Expression and regulation of interleukin-9 in chronic rhinosinusitis.

The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that interleukin (IL)-9 is vital in eliciting inflammatory response, stimulating cell proliferation and preventing apoptosis, through binding to the IL-9 receptor (IL-9R). However, little is known about the roles of both molecules in the etiology of CRS. Therefore, this study aimed to assess IL-9 and IL-9R expression and determine their roles in the pathophysiology of CRS. Immunohistochemistry was used to assess IL-9 and IL-9R immunolabeling. In addition, Western blotting and real-time polymerase chain reaction (PCR) were used for IL-9 and IL-9R protein and mRNA level quantitation, respectively, in CRS and control subjects. Furthermore, the effects of various stimulators at different concentrations and time on IL-9 were evaluated using nasal explant cultures. IL-9 and IL-9R were overexpressed in CRS, especially in CRS with nasal polyps. Interestingly, IL-9 expression was closely related to that of IL-9R. In addition, IL-9 mRNA levels were increased by treatment with IL-4, IL-17A, IL-1beta, and the IL-4 and transforming growth factor (TGF) beta1 combination, but suppressed by interferon gamma and IL-27. IL-9 and IL-9R were overexpressed in CRS at both protein and mRNA levels. In addition, IL-4, IL-17A, IL-1beta, and the IL-4 and TGF-beta1 combination contributed to increased IL-9 levels. Our findings indicate that IL-9 may play a proinflammatory role after IL-9R binding to induce mucosal epithelial cell growth, gland epithelial cell proliferation, and inflammatory cell infiltration in CRS. Future studies are required to further define the role of IL-9 in CRS etiology.