Abstract:
:Sphingolipids play a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the precise roles of sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, and its receptor modulation in COPD. In this study, we demonstrated that the S1P receptor modulator ONO-4641 induced the expansion of lung CD11b+Gr-1+ cells and lymphocytopenia in naive mice. ONO-4641-expanded CD11b+Gr-1+ cells showed higher arginase-1 activity, decreased T cell proliferation, and lower IFN-γ production in CD3+ T cells, similar to the features of myeloid-derived suppressor cells. ONO-4641 treatment decreased airspace enlargement in elastase-induced and cigarette smoke-induced emphysema models and attenuated emphysema exacerbation induced by post-elastase pneumococcal infection, which was also associated with an increased number of lung CD11b+Gr-1+ cells. Adoptive transfer of ONO-4641-expanded CD11b+Gr-1+ cells protected against elastase-induced emphysema. Lymphocytopenia observed in these models likely contributed to beneficial ONO-4641 effects. Thus, ONO-4641 attenuated murine pulmonary emphysema by expanding lung CD11b+Gr-1+ cell populations and inducing lymphocytopenia. The S1P receptor might be a promising target for strategies aimed at ameliorating pulmonary emphysema progression.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Asakura T,Ishii M,Namkoong H,Suzuki S,Kagawa S,Yagi K,Komiya T,Hashimoto T,Okamori S,Kamata H,Tasaka S,Kihara A,Hegab AE,Hasegawa N,Betsuyaku Tdoi
10.1038/s41385-018-0077-5subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1606-1620issue
6eissn
1933-0219issn
1935-3456pii
10.1038/s41385-018-0077-5journal_volume
11pub_type
杂志文章abstract::Bacille Calmette-Guérin (BCG) is the only licenced tuberculosis (TB) vaccine, but has limited efficacy against pulmonary TB disease development and modest protection against extrapulmonary TB. Preventative antibiotic treatment for Mycobacterium tuberculosis (Mtb) infections in high-prevalence settings is unfeasible du...
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pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Mucosal immunology
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journal_title:Mucosal immunology
pub_type: 杂志文章
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journal_title:Mucosal immunology
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journal_title:Mucosal immunology
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journal_title:Mucosal immunology
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journal_title:Mucosal immunology
pub_type: 评论,杂志文章,评审
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