Eosinophils Modulate CD4⁺T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma

Abstract

Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of asthma. The supernatant of the eosinophil culture was found to significantly increase the levels of interleukin (IL)-4 and IL-5 in the supernatant of CD4+ T cells co-cultured with DCs. HMGB1 levels increased in the supernatant of the eosinophil culture stimulated with IL-5. Anti-HMGB1 antibodies significantly attenuated increases of IL-4 and IL-5 levels in the supernatant of CD4+ T cells co-cultured with DCs that were induced by the supernatant of the eosinophil culture. In addition, anti-HMGB1 antibodies significantly attenuated the expressions of activation markers (CD44 and CD69) on CD4+ T cells. Our data suggest that eosinophils modulate CD4+ T cell responses via HMGB1 in the pathogenesis of asthma.

Year in review 2015: Asthma and chronic obstructive pulmonary disease

“…In support, sputum HMGB1 was found to be elevated and directly correlated with asthma severity in children . Recent data also suggest that eosinophils modulate CD4 + T cell responses via HMGB1 in the pathogenesis of asthma …”

“…44 Recent data also suggest that eosinophils modulate CD4 + T cell responses via HMGB1 in the pathogenesis of asthma. 45 Sirtuin 1 (SIRT1), a member of the silent information regulator 2 family, belongs to class III histone deacetylase and is associated with airway inflammation and hyperresponsiveness in allergic asthma. 46 Serum SIRT1 levels were found to be significantly elevated in asthmatic patients, positively correlated with total IgE levels and negatively correlated with pulmonary function.…”

Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats

“…No previous data were reported regarding the effect of cinnarizine on eosinophil activation, but the role of eosinophils in the progression of the inflammatory and immunological arms of bronchial asthma was recently reported [5,51]. Eosinophils exert their deleterious effects on asthma progression through the release of several pro-inflammatory mediators including cytokines and others [52].…”

“…Bronchial asthma is associated with infiltration of eosinophils, mast cells and activated T-helper lymphocytes, leading to increased release of allergic and inflammatory mediators including histamine, leukotrienes, tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5) and nitric oxide [3,4]. Eosinophils play a critical role recently reported as modulation of the responsiveness of CD4 + T-lymphocytes [5]. Massive amounts of histamine are released from mast cells upon their stimulation by occupied IgE antibodies [6].…”

A Player and Coordinator: The Versatile Roles of Eosinophils in the Immune System

“…This regulatory effect on memory cells could be of crucial significance in Th2 immune response elicited by re-exposure of allergens or re-infection of parasites. Moreover, recent findings with in vitro experiments have indicated that eosinophils can modulate CD4+ T-cell responses via eosinophil-secreted HMGB1 in the pathogenesis of asthma [70].…”