High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses.
High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses.
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高迁移率基团核小体结合蛋白 1 充当警报素，对于脂多糖诱导的免疫反应至关重要。
DOI：
10.1084/jem.20101354
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发表时间：
2012-01-16
期刊：
影响因子：
--
通讯作者：
Oppenheim JJ
中科院分区：
文献类型：
--
作者：
Yang D;Postnikov YV;Li Y;Tewary P;de la Rosa G;Wei F;Klinman D;Gioannini T;Weiss JP;Furusawa T;Bustin M;Oppenheim JJ
HMGN 1是一种新型的alarmin，通过TLR 4发出信号，并且是LPS诱导的体内免疫应答所必需的。Alarmins是能够促进抗原呈递细胞（APC）（包括树突状细胞（DC））的募集和激活的内源性介质，其可以潜在地警告宿主防御危险信号。然而，alarmin与诱导适应性免疫应答的相关性仍有待证明。在这项研究中，我们报告了HMGN 1（高迁移率组核小体结合蛋白1）作为一种新的alarmin的鉴定，并证明它有助于诱导抗原特异性免疫反应。HMGN 1通过TLR 4（Toll样受体4）诱导DC成熟，在注射部位募集APC，以及在DC中激活NF-κB和多种丝裂原活化蛋白激酶。HMGN 1在与抗原共同施用时促进抗原特异性免疫应答，并且当在脂多糖（LPS）存在下用抗原免疫时，Hmgn 1 −/−小鼠产生的抗原特异性抗体和T细胞应答大大降低。Hmgn 1 −/−小鼠产生抗原特异性免疫应答的能力受损，同时伴有免疫部位DC募集不足和炎性细胞因子产生减少。骨髓嵌合体实验表明，来自非白细胞的HMGN 1是诱导抗原特异性抗体和T细胞反应的关键。因此，细胞外HMGN 1作为一种新的报警蛋白，对LPS诱导的先天性和适应性免疫应答的发展至关重要。
HMGN1 is a novel alarmin that signals through TLR4 and is required for LPS-induced immune responses in vivo. Alarmins are endogenous mediators capable of promoting the recruitment and activation of antigen-presenting cells (APCs), including dendritic cells (DCs), that can potentially alert host defense against danger signals. However, the relevance of alarmins to the induction of adaptive immune responses remains to be demonstrated. In this study, we report the identification of HMGN1 (high-mobility group nucleosome-binding protein 1) as a novel alarmin and demonstrate that it contributes to the induction of antigen-specific immune responses. HMGN1 induced DC maturation via TLR4 (Toll-like receptor 4), recruitment of APCs at sites of injection, and activation of NF-κB and multiple mitogen-activated protein kinases in DCs. HMGN1 promoted antigen-specific immune response upon co-administration with antigens, and Hmgn1−/− mice developed greatly reduced antigen-specific antibody and T cell responses when immunized with antigens in the presence of lipopolysaccharide (LPS). The impaired ability of Hmgn1−/− mice to mount antigen-specific immune responses was accompanied by both deficient DC recruitment at sites of immunization and reduced production of inflammatory cytokines. Bone marrow chimera experiments revealed that HMGN1 derived from nonleukocytes was critical for the induction of antigen-specific antibody and T cell responses. Thus, extracellular HMGN1 acts as a novel alarmin critical for LPS-induced development of innate and adaptive immune responses.
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影响因子：
30.8
作者：
Calogero, S;Grassi, F;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
11.2
作者：
Birger, Y;Catez, F;Bustin, M
通讯作者：
Bustin, M
影响因子：
3.2
作者：
Piazza M;Damore G;Costa B;Gioannini TL;Weiss JP;Peri F
通讯作者：
Peri F
影响因子：
4.4
作者：
Ohashi, K;Burkart, V;Kolb, H
通讯作者：
Kolb, H
影响因子：
2.7
作者：
Mohamed, OA;Bustin, M;Clarke, HJ
通讯作者：
Clarke, HJ