ILC2s Induce Adaptive Th2-Type Immunity in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Min Jiang,Kaixiu Cao,Zheng Li,Fengbo Zhang,Fengsen Li,Huifang Liu,Jianbing Ding,Jing Wang

doi:10.1155/2019/3140183

Abstract

To investigate the effect of ILC2s on Th2-type adaptive immunity during the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the study enrolled healthy people, stable COPD patients, and AECOPD patients. Flow cytometry was used to detect Th1, Th2, and ILC2 in the peripheral blood and CD80 and MHC II levels on ILC2. The mRNA levels of GATA3, RORα, and CRTH2 of ILC2s were detected by RT-PCR. In addition, ILC2s from the peripheral blood of AECOPD patients were cocultured with CD4+ T cells from the peripheral blood of healthy controls. Cytokine levels in serum of the three groups and the in vitro coculture supernatants were measured by ELISA. Compared with the stable COPD group or the healthy control group, Th2 in the peripheral blood of AECOPD group increased dramatically, inducing an increase of Th2/Th1 ratio in AECOPD patients. Meanwhile, the level of IL-4 in the serum of this group was also increased. However, we also detected ILC2s in the peripheral blood of the AECOPD group and found that it was also increased, alone with the increased GATA3, RORα, and CRTH2 mRNA levels. We also found that the CD80 and MHC II on ILC2 were significantly upregulated and the proportion of MHC II+ ILC2 cells was significantly positively correlated with the proportion of Th2 cells in AECOPD patients. To further demonstrate the effect of ILC2 on Th2 cells, we cocultured ILC2 with CD4+ T cells in vitro, which also showed a significant increase of Th2 ratio as well as Th2-associated cytokines IL-4, IL-5, and IL-13. However, we found that this effect of ILC2s on Th2 cells could be inhibited by the addition of anti-MHC II. The Th2/Th1 balance shifts to Th2 in AECOPD. ILC2s may function as APC by the upregulation of MHC II and regulate adaptive immunity shift to Th2-type response in AECOPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the respiratory tract characterized by persistent incomplete reversible airflow limitation [1, 2]
We found that ILC2 could play as antigen-presenting cells (APC) by upregulating CD80 and MHC II molecules, thereby regulating Th2-type immune response in acute exacerbation of COPD (AECOPD)
The Th2/Th1 ratio was decreased in patients with stable COPD whereas it increased in patients with AECOPD, indicating that the Th2/Th1 balance is shifted to Th1 response in stable COPD while it shifted to Th2 response in AECOPD

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the respiratory tract characterized by persistent incomplete reversible airflow limitation [1, 2]. Recurrent AECOPD is an important factor in promoting the progression of COPD, leading to a decline in the quality of life of patients and an increase in mortality [3,4,5,6]. Lower respiratory tract bacterial infection is an important factor in the occurrence of AECOPD, which can lead to immune dysfunction. Studies found that the abnormality of T cell subsets is the main cause of immune dysfunction in COPD [7,8,9] and Th1/Th2 imbalance may be one of the causes of AECOPD [10]. It is reported that the activation and proliferation of Th2 cells in the peripheral blood of patients with AECOPD were more obvious, resulting in a significant downregulation of Th1/Th2 ratio and a shift to Th2 responses [11]. The cause of the shift of the adaptive immunity to the Th2-type immune response in the AECOPD remains unclear

Methods

Results

Conclusion