期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 96, 期 3-4, 页码 249-263出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-017-1614-5
关键词
Adenoviral vector; Allergic asthma; Cytokines; Immunization; Mycobacterial antigens
资金
- National Natural Science Foundation of China [91442102, 31200693, 31470892, 31300764]
- Guangzhou Health Care and Cooperative Innovation Major Project [201508020252, 201604020006]
- Pearl River S&T Nova Program of Guangzhou [201506010076]
- CAS Youth Innovation Promotion Association [2014328]
Current treatments for allergic asthma primarily ameliorate symptoms rather than inhibit disease progression. Regulating the excessive T helper type 2 (Th2) responses may prevent asthma exacerbation. In this study, we investigated the protective effects of Ad5-gsgAM, an adenovirus vector carrying two mycobacterial antigens Ag85A and Mtb32, against allergic asthma. Using an ovalbumin (OVA)-induced asthmatic mouse model, we found that Ad5-gsgAM elicited much more Th1-biased CD4(+)T and CD8(+)T cells than bacillus Calmette-Guerin (BCG). After OVA challenge, Ad5-gsgAM-immunized mice showed significantly lowered airway inflammation in comparison with mice immunized with or without BCG. Total serum immunoglobulin E and pulmonary inducible-nitric-oxide-synthase were efficiently reduced. The cytokine profiles in bronchial-alveolar-lavage-fluids (BALFs) were also modulated, as evidenced by the increased level of interferon-gamma (IFN-gamma) and the decreased level of interleukin (IL)-4, IL-5, and IL-13. Anti-inflammatory cytokine IL-10 was sharply increased, whereas pro-inflammatory cytokine IL-33 was significantly decreased. Importantly, exogenous IL-33 abrogated the protective effects of Ad5-gsgAM, revealing that the suppression of IL-33/ST2 axis substantially contributed to protection against allergic inflammation. Moreover, regulatory T cells were essential for regulating aberrant Th2 responses as well as IL-33/ST2 axis. These results suggested that modulating the IL-33/ST2 axis via adenovirus-vectored mycobacterial antigen vaccination may provide clinical benefits in allergic inflammatory airways disease.
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