Allergy Asthma Immunol Res.  2015 Mar;7(2):190-194. 10.4168/aair.2015.7.2.190.

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

• Shim EJ
• Chun E
• Lee HS
• Bang BR
• Cho SH
• Min KU
• Park HW

• KMID: 2365548
• DOI: http://doi.org/10.4168/aair.2015.7.2.190

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.

Keyword

Asthma; eosinophil; high-mobility group box 1 protein (HMGB1); T cell

MeSH Terms

Antibodies
Asthma*
Dendritic Cells
Eosinophils*
HMGB1 Protein
Inflammation
Interleukin-4
Interleukin-5
Interleukins
T-Lymphocytes
Antibodies
HMGB1 Protein
Interleukin-4
Interleukin-5
Interleukins

Figure

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  Fig. 1 IL-4 and IL-5 levels in the supernatant of CD4+ T cells co-cultured with dendritic cells after incubation with the supernatant of the eosinophil culture.

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  Fig. 2 HMGB1 levels in the supernatant of the eosinophil culture before and after IL-5 stimulation.

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  Fig. 3 IL-4 and IL-5 levels in the supernatant of CD4+ T cells co-cultured with dendritic cells after incubation with the supernatant of the eosinophil culture alone or plus anti-HMGB1 antibodies.

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  Fig. 4 CD44 and CD69 expressions on the CD4+ T cells after incubation with the eosinophil culture supernatant alone or with the eosinophil culture supernatant plus anti-HMGB1 antibodies. Relative expression was represented as a ratio compared to the mean fluorescence intensity of each molecule treated with media only.

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