Role of IL‐9 and IL‐10 in the pathogenesis of chronic spontaneous urticaria through the JAK/STAT signalling pathway

Abstract

This study investigated the role of interleukin (IL)-9 and IL-10 in the pathogenesis of chronic spontaneous urticaria (CSU). Autologous serum skin test and histamine release test were performed in CSU patients and normal subjects. Kunming mice were used to develop a mouse model for CSU. We induced IL-9 overexpression, IL-10 overexpression, and JAK/STAT pathway inhibition as well as a combination of all three conditions in CSU and control mice. Eosinophils in the skin tissues, inflammatory cytokine expression, and distribution of T lymphocyte subsets in peripheral blood of mice were detected. Expression patterns of IL-9, IL-10, STAT3, JAK2, and INF-γ in clinical samples and mice were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The positive rate of autologous serum skin test and the histamine release rate of CSU patients, compared with normal subjects, were apparently elevated. Compared with controls, mice with CSU experienced longer duration and higher frequency of pruritus and demonstrated enhanced levels of CD8 + , the ratio of CD4 + /CD8 + , number of eosinophils, and inflammatory cytokine expression in serum as well as activated JAK/STAT signalling pathway; at the same time, levels of CD4 + and INF-γ were reduced. This trend was found in CSU mice overexpressing IL-9 and IL-10 when compared with the CSU mice without treatment. In contrast, JAK/STAT inhibition reversed the above trend.Overall, our study suggests that IL-9 and IL-10 contribute to CSU development via activation of the JAK/STAT signalling pathway. K E Y W O R D S chronic spontaneous urticaria, inflammation, interleukin-9, interleukin-10, JAK/STAT signalling pathway 1 | INTRODUCTION Chronic urticaria (CU), defined as urticaria that has been continuously or intermittently existing for more than 6 weeks, has an estimated prevalence in the general population of 0.5% to 5% and an incidence of 1.4% per year. 1 Patients where no underlying cause for CU was identified were diagnosed as chronic idiopathic urticaria (mainly used in North America) or chronic spontaneous urticaria (CSU). 2 CSU is caused by degranulation of basophils and/or cutaneous mast cells, which results in effective vasoactive mediators released to induce vasodilatation and increased capillary permeability, leading to erythema and wheal formation. 3 Wheal is an elementary dermatological lesion, characterized by itchiness and the presences of central oedema in various sizes, with a reflex erythema encircling and ephemeral

Analysis of the Transcriptional Activity of Immune Response Genes in the Blood of Patients with Acute Urticaria

“…However, in CU, the expression of IL-10 was not affected [37]. There is no systemic link between data on the expression of IL-10 in the experiment and patients with CU compared with control or mRNA levels in PBMCs [38].…”

New Biological Treatment Options in CSU

“…In a recent study using Kunming mice (a model of CSU), a longer duration and higher intensity of pruritus was demonstrated to be in association with enhanced levels of eosinophils, inflammatory cytokine expression and activated the JAK/STAT signaling pathway. This was found to be in mice overexpressing IL-9 and IL-10, contributing to the development of CSU by signaling the JAK/STAT pathway [14]. Commensurate with this, is the later finding of antigen/disease-specific autoreactive CD4 + T cells that target FcεRIα in most patients with CSU, with a cytokine secretion profile typical of aTh1 immune response.…”

Integrated bioinformatics approach to understand immune-related key genes and pathways in chronic spontaneous urticaria

“…In addition, OSMR gene silencing can signi cantly reduce the content of in ammatory factors, eosinophils, mRNA and protein expression of Jak/STAT3 signaling pathway related genes, promote cell proliferation and migration, and inhibit epithelial cell apoptosis to suppress CSU mouse model autoimmunity reaction [24]. Another study also found that IL9 and IL10 can promote the development of CSU by activating the Jak/STAT3 signaling pathway [25]. Interestingly, our GSEA enrichment results on two data sets showed high expression of IL6/Jak/STAT3 pathway in the CSU patient group.…”