TRIM41 contributes to the pathogenesis of airway allergy by compromising dendritic cells’ tolerogenic properties

Summary: Dendritic cells (DC) play a crucial role in the initiation of immune responses. TRIM41, an E3 ubiquitin ligase, can facilitate targeting protein degradation. The purpose of this study is to analyze the role of TRIM41 in the pathogenesis of airway allergy (AA) and the impact of regulating TRIM41 on suppressing AA. We observed that the airway DCs of AA mice had a higher expression of Trim41. The expression of Trim41 in airway DCs was associated with the DCs’ tolerogenic functions of AA mice. The AA responses, including increased amounts of eosinophil peroxidase, mast cell protease-1, Th2 cytokines, and specific IgE in bronchoalveolar lavage fluids, were positively correlated with the Trim41 expression in mouse airway DCs. TRIM41 induced c-Maf degradation and interfered with the Il10 expression in airway DCs, which could be counteracted by inhibiting TRIM41. Regulation of TRIM41 mitigated experimental AA responses

Nasal mucosal fibroblasts produce IL-4 to induce Th2 response

Th2 polarization is essential for the pathogenesis of allergic rhinitis (AR). Th2 polarization's mechanism requires further understanding. IL-4 is the primary cytokine involved in Th2 response. Fibroblasts play a role in immune regulation. This study aims to elucidate the role of nasal mucosal fibroblast-derived IL-4 in the induction of Th2 responses. Nasal mucosal tissues were obtained from surgically removed samples from patients with nasal polyps, whether with or without AR. Fibroblasts were isolated from the tissues by flow cytometry cell sorting, and analyzed by RNA sequencing (RNAseq). The data from RNAseq showed that nasal fibroblasts expressed genes of GATA3, CD80, CD83, CD86, STAT6, IL2, IL4, IL5, IL6, IL13 and costimulatory factor. The data were verified by RT-qPCR. The level of gene activity was positively correlated with those of AR-related cytokines present in nasal secretions. Nasal fibroblasts release IL-4 upon activation. Nasal fibroblasts had the ability to transform naive CD4 + T cells into Th2 cells, which can be eliminated by inhibiting IL-4 receptor or CD28 in CD4 + T cells. To sum up, nasal mucosal fibroblasts produce IL-4, which can induce Th2 cell development. The data implicate that nasal fibroblasts are involved in the pathogenesis of nasal allergy

Surface co-stimulatory molecule expression was analyzed by gating on CD11c cell populations by FACS

A, representative histograms showing the percentage of co-stimulatory molecules expression by CD11c+ cells. Solid lines, specific staining; shaded histograms, appropriate isotype controls. B, Average Mean Fluorescent Intensity (MFI) of co-stimulatory markers. Data are representative of three independent experiments.<p><b>Copyright information:</b></p><p>Taken from "CD11c+ antigen presenting cells from the alveolar space, lung parenchyma and spleen differ in their phenotype and capabilities to activate naïve and antigen-primed T cells"</p><p>http://www.biomedcentral.com/1471-2172/9/48</p><p>BMC Immunology 2008;9():48-48.</p><p>Published online 13 Aug 2008</p><p>PMCID:PMC2527294.</p><p></p

ER stress modulates the immune regulatory ability in gut M2 cells of patients with ulcerative colitis

Summary: This study aims to characterize the impaired immune regulatory function of Mφ obtained from UC patient colon lavage fluid (CLF). Mφs were the largest proportion (21.3 4.0%) of the CLF-derived cellular components. Less abundant and weaker immune suppressive function were observed in M2 Mφs (M2 cells) of the ulcerative colitis (UC) group. High levels of endoplasmic reticulum (ER) stress associated molecules were detected in UC M2 cells. The spliced X box binding protein-1 (XBP1) gene was negatively correlated with programmed death ligand-1 (PD-L1) in UC M2 cells. XBP1 promoted the expression of ring-finger protein 20 (Rnf20) in M2 cells. Rnf20 reduced PD-L1 abundance in UC M2 cells and impaired the immune suppressive ability. Inhibition of Rnf20 restored the immune regulating capacity of M2 cells and suppressed experimental colitis

Probiotics and AC regulates the intestinal microbial composition and diversity.

<p>(A) PCA in the 50^th day, the 100^th day and the 150^th day were performed based on the genera abundance of the microbial genomes. (B) Main genus composition was a percentage of total assigned sequences. (C) Bacterial phyla distribution as a percentage of total sequences. (D) Heatmap represents a sample of a color, abundance of a genus is a longitudinal sample clustering situation, reflecting on the case of multiple samples at the level of community composition similarity. All presented results are statistically significant (p<0.05) as assessed by the Wilcoxon test.</p

An association between elevated telomerase reverse transcriptase expression and the immune tolerance disruption of dendritic cells

Abstract Background To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs. Methods The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting. Results The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR. Conclusions Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR

CD11c APC populations were isolated from BAL, lung parenchyma and the spleen and pulsed with M

Tb CF protein or infected with live mycobacteria. APCs were then co-cultured with CD4+ or CD8+ T cells that were purified from the mice that were infected by live mycobacteria for 17 days (diagram). Cells were co-cultured for 24 h and IFN-γ-secreting T cells were determined by ELISPOT assay. A, IFN-γ-secreting CD4+ T cells. B, IFN-γ-secreting CD8+ T cells. Data are expressed as the mean value ± SD of triplicate samples and representative of two independent experiments. ‡p < 0.05 compared to the corresponding mycobacterial BCG-infected APCs; #p < 0.05 compared to the corresponding spleen data.<p><b>Copyright information:</b></p><p>Taken from "CD11c+ antigen presenting cells from the alveolar space, lung parenchyma and spleen differ in their phenotype and capabilities to activate naïve and antigen-primed T cells"</p><p>http://www.biomedcentral.com/1471-2172/9/48</p><p>BMC Immunology 2008;9():48-48.</p><p>Published online 13 Aug 2008</p><p>PMCID:PMC2527294.</p><p></p