九州大学 生体防御医学研究所

下記の通り、Mari Shinohara先生によるセミナーを開催致します。多くの方々のご来聴をお待ちしております。

演題

Innate immunity and CNS autoimmune disease.

演者

Mari Shinohara, PhD
Associate Professor
Department of Immunology, Duke University

日時

2016年10月4日（火）　Oct. 4 (Tue), 2016
17：00～18：00

場所

病院キャンパス内　生体防御医学研究所 本館1階 会議室
以下の地図の24番です。
（https://www.kyushu-u.ac.jp/f/28545/hospital_jp.pdf）

Seminar Room, Main Building 1F, Medical Institute of Bioregulation
No.24 on the following linked map.
（https://www.kyushu-u.ac.jp/f/28551/hospital_en.pdf）

要旨

Innate immunity has been developed to protect hosts from microbial infections during evolution. However, the recent advancement in understanding innate immunity revealed that host protection from microbes is not the only role of innate immunity. The great impact of innate immunity on a wide variety of diseases and pathogenic conditions is now widely known. In this presentation, I would like to focus on a critical role of inflammation triggered by the innate immune system in the development autoimmunity in the central nervous system (CNS) by using experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis (MS), and considered to be a T cell-mediated disease.

Our previous studies described that the innate immune system mediates the efficacy of IFNβ treatment in MS and EAE. In particular, IFNβ inhibits Th17 responses and NLRP3 inflammasome activation^{1, 2} and the inhibitions eventually ameliorate EAE^{1, 3}. Indeed, the NLRP3 inflammasome is a pathogenic innate immunity sensor in EAE³. However, we have recently found that the NLRP3 inflammasome is dispensable in EAE induced by strong stimulation of innate immunity. This subtype of EAE is resistant to IFNβ treatment but ameliorated by the blockade of LTβR or CXCR2. In other words, the NLRP3 inflammasome is bypassed and an alternative pathway depending on the LTβR-CXCR2 axis becomes critical when innate immunity is strongly activated⁴. I will further discuss how the pathology of the NLRP3 inflammasome-independent and IFNβ-resistant EAE subtype is distinct from typical EAE. One of the notable phenotypes of the EAE subtype is characterized by neuronal damages by enhanced expression of semaphorin-6B in CD4⁺ T cells⁴.

References

1. Inoue, M., et al. Interferon-beta therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome. Sci Signal 5, ra38 (2012).
2. Shinohara, M.L., et al. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 29, 68-78 (2008).
3. Inoue, M., et al. NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 109, 10480-10485 (2012).
4. Inoue, M., et al. Lymphotoxin-β receptor and CXCR2 induce an IFNβ-resistant EAE subtype with CNS neuronal damages mediated by semaphorin 6B. Nat Neurosci. in press.

連絡先

生体防御医学研究所　分子免疫学分野
山崎　晶　092(642)4614