Increased Proportion of Dual-Positive Th2-Th17 Cells Promotes a More Severe Subtype of Asthma.

Wenjin Sun,Aijun Jia,Shaokun Liu,Yu Yuan,Lulu Qiu,Xudong Xiang,Bing Xiao,Libing Ma,Jingsi Jia,Qingping Zeng,Akiteru Goto

doi:10.1155/2021/9999122

Abstract

Asthma is a heterogeneous disease, and abnormal activation of T cells is the driving link of asthma's pathophysiological changes. Dual-positive Th2–Th17 cells, as newly discovered T-helper cells, have the functions of Th2 and Th17 cells and can coproduce Th2 and Th17 cytokines. Previous studies have shown that dual-positive Th2–Th17 cells increase the chances of asthma and correlate with asthma severity. However, the exact role of dual-positive Th2–Th17 cells in asthma is not known. Since there is no mature differentiation method for dual-positive Th2–Th17 cells, the present study aimed to clarify the strict differentiation conditions and reveal how dual-positive Th2–Th17 cells regulate asthma phenotypes. In this study, we confirmed that IL-1β, IL-6, anti-IFN-γ, and IL-21 promoted biphenotypic cell differentiation. Moreover, more proportion of dual-positive Th2–Th17 cells can be obtained by conditioned differentiation of mouse CD4+ T cells after classical allergic asthma modeling. Before asthma modeling, adoptive dual-positive Th2–Th17 cells promoted T cells to differentiate into the same biphenotype cells and exacerbated the severity of asthma. Together, our results clarify the differentiation conditions of dual-positive Th2–Th17 cells and further confirm that it stimulates asthma T cells to differentiate into the same biphenotype cells, leading to exacerbation of asthma.

Highlights

Bronchial asthma is a chronic inflammatory disease of the airways [1, 2]
There is no mature differentiation method for dual-positive 2– 17 cells. e current controversy is whether IL-21 or IL-23 is the necessary cytokines for the differentiation of dual-positive 2– 17 cells, in the presence of cytokines IL-1β, IL-6, and anti-IFN-c [11, 12]
We performed the following experiments: CD4+ T cells were isolated 3 days after OVA intervention (Figure 1(a)), 20 ng/ mL IL-1β, 20 ng/mL IL-6, 20 ng/mL anti-IFN-c, and 10 ng/ mL IL-21 or 10 ng/mL IL-23 were added for differentiation intervention, and flow cytometry was used to detect the effects of different intervention cytokines and intervention time on the differentiation of cells in each group

Summary

Introduction

Different subtypes can be seen in asthma patients due to their heterogeneity [3,4,5]. As an important part of the pathogenesis of asthma, the abnormal activation of T cells is the initiating factor leading to a series of pathophysiological changes [6, 7]. A large number of studies have proved that T-helper cells have plastic deformability and transform each other under different stimuli [8,9,10]. E presence of dual-positive 2– 17 cells was first discovered in 2010 [11]. Further studies have shown that the proportion of dual-positive 2– 17 cells in asthmatic patients is significantly higher than that of healthy people [12]. As a newly discovered T-helper cell, no further study on dual-positive

Methods

Results

Conclusion