Eosinophils Modulate CD4(+) T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma.
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.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Eun-Jin
EJ
Shim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Eunyoung
E
Chun
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Hyun-Seung
HS
Lee
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Bo-Ram
BR
Bang
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Sang-Heon
SH
Cho
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Kyung-Up
KU
Min
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University College of Medicine, Seoul, Korea.
Heung-Woo
HW
Park
Asthma; T cell; eosinophil; high-mobility group box 1 protein (HMGB1)