期刊
ALLERGY
卷 75, 期 5, 页码 1133-1145出版社
WILEY
DOI: 10.1111/all.14129
关键词
airway; house dust mite; inflammation; macrophage; progranulin
资金
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT (MSIT) [NRF-2017R1C1B5018376, NRF2018R1A2B6006606]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health and Welfare, Republic of Korea [HI14C2628]
- Basic Science Research Program through National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2017R1A6A3A11028289]
- National Research Foundation of Korea (NRF) MRC - Korean government (MSIT) [2018R1A5A2020732]
Background Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, and we investigated the role of PGRN in allergic airway inflammation. Methods Production of PGRN and various type 2 cytokines was evaluated in mouse airways exposed to house dust mite allergen, and main cellular sources of these molecules were investigated using macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage-derived PGRN-deficient mice and NKT cell knockout mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation. Results PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN-induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRN-deficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period. Conclusion The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.
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