The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

Zhou, Bingjing; Li, Jie; Li, Jie; Li, Zhu; Peng, Cong

doi:10.3389/fimmu.2022.879754

Cited by 39 publications

(49 citation statements)

References 217 publications

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“…Apart from that, classical monocytes may play a central role in severe COVID-19 ( 38 ). In addition, the researchers found that in CU, Toll-like receptors agonists could induce the expression of TFs of monocytes, and the TFs increased vascular permeability in a histamine-independent way, leading to the formation of a wheal ( 39 ). In some way, these results may hint that the shared DEGs could play a role in the immunoregulation of CU and COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics to identify potential key biomarkers for COVID-19-related chronic urticaria

Zhang

Feng²,

Zou³

et al. 2022

Front. Immunol.

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BackgroundA lot of studies have revealed that chronic urticaria (CU) is closely linked with COVID-19. However, there is a lack of further study at the gene level. This research is aimed to investigate the molecular mechanism of COVID-19-related CU via bioinformatic ways.MethodsThe RNA expression profile datasets of CU (GSE72540) and COVID-19 (GSE164805) were used for the training data and GSE57178 for the verification data. After recognizing the shared differently expressed genes (DEGs) of COVID-19 and CU, genes enrichment, WGCNA, PPI network, and immune infiltration analyses were performed. In addition, machine learning LASSO regression was employed to identify key genes from hub genes. Finally, the networks, gene-TF-miRNA-lncRNA, and drug-gene, of key genes were constructed, and RNA expression analysis was utilized for verification.ResultsWe recognized 322 shared DEGs, and the functional analyses displayed that they mainly participated in immunomodulation of COVID-19-related CU. 9 hub genes (CD86, FCGR3A, AIF1, CD163, CCL4, TNF, CYBB, MMP9, and CCL3) were explored through the WGCNA and PPI network. Moreover, FCGR3A, TNF, and CCL3 were further identified as key genes via LASSO regression analysis, and the ROC curves confirmed the dependability of their diagnostic value. Furthermore, our results showed that the key genes were significantly associated with the primary infiltration cells of CU and COVID-19, such as mast cells and macrophages M0. In addition, the key gene-TF-miRNA-lncRNA network was constructed, which contained 46 regulation axes. And most lncRNAs of the network were proved to be a significant expression in CU. Finally, the key gene-drug interaction network, including 84 possible therapeutical medicines, was developed, and their protein-protein docking might make this prediction more feasible.ConclusionsTo sum up, FCGR3A, TNF, and CCL3 might be potential biomarkers for COVID-19-related CU, and the common pathways and related molecules we explored in this study might provide new ideas for further mechanistic research.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics to identify potential key biomarkers for COVID-19-related chronic urticaria

Zhang

Feng²,

Zou³

et al. 2022

Front. Immunol.

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“…Understanding these principles is complex, and according to current knowledge, aside from humoral (autoantibodies), it also involves cellular responses (auto-reactive T cells) and the dysfunction of adaptive cellular immunity [ 19 , 20 ]. According to current literature data, crucial pathogenetic factors/events for CSU are the activation of mast cells, basophils, T cells, and eosinophils, as well as increased vascular permeability and vasodilation, activation of coagulation pathways and autoimmunity processes, and finally, the release of mast cell mediators [ 21 ]. Thus, CSU involves the participation of both innate immunity (mast cells, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer [NK] cells, innate lymphocytes [ILC], complement factors) and adaptive immunity (Th1 and, Th2 cells, Th9 cells, Th17 cells, regulatory T cells [Treg cells], B cells, antibodies), wherein mast cells link innate and adaptive immunity.…”

Section: Immunopathogenesis Of Chronic Urticarial and Immune Changes ...mentioning

confidence: 99%

“…Thus, CSU involves the participation of both innate immunity (mast cells, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer [NK] cells, innate lymphocytes [ILC], complement factors) and adaptive immunity (Th1 and, Th2 cells, Th9 cells, Th17 cells, regulatory T cells [Treg cells], B cells, antibodies), wherein mast cells link innate and adaptive immunity. Mast cells have various roles: they induce/modulate T-cell activation and polarization; stimulate B cells to produce IgE (through IL-4 and IL-13); produce mediators (e.g., TNFα), which act on vascular endothelial cells’ up-regulation and adhesion molecules‘ expressions, which promote the recruitment of T cells; allergen-specific Th2 cells stimulate B cell production of IgE, which stimulates/activates mast cells and basophils [ 21 ]. In the skin tissue of urticarial CSU lesions, mast cells predominate, and there are increased numbers of basophils, eosinophils, macrophages, neutrophils and T cells, while there are decreased numbers of Th17 cells.…”

Section: Immunopathogenesis Of Chronic Urticarial and Immune Changes ...mentioning

confidence: 99%

“…In the skin tissue of urticarial CSU lesions, mast cells predominate, and there are increased numbers of basophils, eosinophils, macrophages, neutrophils and T cells, while there are decreased numbers of Th17 cells. In the serum of CSU patients, decreased numbers of Treg cells (among PBMC) are found, while increased IL-17 serum levels are seen (produced by Th17) [ 21 ]. Mast cells and T cells interact through various contacts, including through their inflammatory mediators and their receptors.…”

Section: Immunopathogenesis Of Chronic Urticarial and Immune Changes ...mentioning

confidence: 99%

“…Thus, histamine mediates the enhancement of Th2 cytokine secretion while inhibiting Th1 cytokine production, maintaining Th1/Th2 cell balance and supporting the dominance of Th2 cells. In addition, mast cells produce cytokines that promote Th2 cell activation, survival and migration (PGD2 and leukotriene E4) [ 21 ].…”

Section: Immunopathogenesis Of Chronic Urticarial and Immune Changes ...mentioning

confidence: 99%

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Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data

Krišto¹,

Lugović-Mihić²,

Muñoz

et al. 2023

Life

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Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of the immune system, it is likely that an alteration of microbiota components (a dysbiosis) could influence the course of chronic spontaneous urticaria (CSU), including disease severity, patient quality of life and treatment outcome. To date, several studies have identified changes in the gut microbiota composition of patients with CSU, though only a few have exhibited metabolic abnormalities associated with gut dysbiosis. The studies on CSU patients predominantly showed that the relative abundance of beneficial bacteria was decreased (Firmicutes and Bacteroides), while that of opportunistic bacteria was increased (Enterobacteria and Proteobacteria). In addition, serum metabolome analysis revealed that gut microbiota-associated alterations in unsaturated fatty acids and the butanoate metabolism pathway may play a role in CSU. These findings are potentially associated with inflammation mediated by the imbalance of Th1/Th2/Th17 cytokines, which might contribute to CSU pathogenesis. Further research in this field could improve clinical, diagnostic, and therapeutic approaches to patients with CSU. By applying new knowledge on gut microbial communities and metabolomics, future CSU therapies could modify the microbiota composition using agents such as probiotics or other similar agents, which, in combination with current standard therapies, could hopefully lead to a reduction in symptoms and an improved quality of life for CSU patients.

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The correlation between Th17/Treg immune dysregulation and the disease severity in chronic spontaneous urticaria patients

Yang

Wang

et al. 2023

Immunity Inflam & Disease

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Objective Chronic spontaneous urticaria (CSU) has a profound impact on the sleep quality, productivity and overall quality of life of affected individuals. This study aimed to investigate the correlation between serum Th17/Treg immune dysregulation and the severity of CSU in patients. Methods Clinical baseline data of 120 CSU patients and matched healthy controls were recorded. The pruritus level, disease severity, and quality of life of CSU patients were assessed using the visual analogue scale, weekly Urticaria Activity Score and chronic urticaria quality of life questionnaire, respectively. The Th17/Treg cell ratio was detected by flow cytometry. ELISA was used to measure the levels of serum Th17 cytokines (IL‐17, IL‐21) and Treg cytokines (TGF‐β1, IL‐35). Pearson's correlation analysis was conducted to examine the associations between these indicators. Results No significant differences were identified in terms of sex, age, and BMI between the two groups. However, CSU patients exhibited a significant increase in the Th17 cell ratio, as well as the elevated serum levels of TGF‐β1, IL‐17 and, IL‐21. Conversely, the proportion of Treg cells and the levels of IL‐35 were remarkably decreased in CSU patients. Peripheral blood Th17 cells were negatively correlated with Treg cells. The severity of pruritus, life quality, and disease severity in CSU patients were positively correlated to Th17 cell ratio, and inversely correlated with Treg cell proportion. Conclusions A positive correlation was found between the percentage of peripheral blood Th17 cell in CSU patients and the pruritus level, life quality, and disease severity. In constrast, there was a negative correlation between the proportion of peripheral blood Treg cells and these clinical parameters.

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The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

Cited by 39 publications

References 217 publications

Integrated bioinformatics to identify potential key biomarkers for COVID-19-related chronic urticaria

Integrated bioinformatics to identify potential key biomarkers for COVID-19-related chronic urticaria

Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data

The correlation between Th17/Treg immune dysregulation and the disease severity in chronic spontaneous urticaria patients

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