Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis.
Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis.
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DOI：
10.1084/jem.20021788
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发表时间：
2003-02-03
期刊：
影响因子：
--
通讯作者：
Kopf M
中科院分区：
文献类型：
--
作者：
Eriksson U;Kurrer MO;Sonderegger I;Iezzi G;Tafuri A;Hunziker L;Suzuki S;Bachmaier K;Bingisser RM;Penninger JM;Kopf M
由心肌炎引起的扩张型心肌病是年轻患者心力衰竭的最常见原因。白介素1受体1型缺陷(IL-1R1−/−)小鼠经α-肌球蛋白多肽(614-629)免疫后，可预防自身免疫性心肌炎。免疫IL-1R1−/−小鼠的CD_4~+T细胞在注射入幼稚的严重联合免疫缺陷小鼠后，增殖不良，不能转移疾病。体外刺激实验表明，IL-1R1CD4+T细胞功能不是先天缺陷，而是树突状细胞对−/−的激活功能受损。因此，在缺乏IL-1受体1型的树突状细胞中，肿瘤坏死因子-α、IL-1、IL-6和IL-12p70的产生减少。事实上，将未成熟的、抗原负载的IL-1R1+/+而不是IL-1R1−/−树突状细胞注射到IL-1R1−/−小鼠体内，通过使IL-1R1−/−+T细胞致病，完全恢复了疾病的易感性。因此，IL-1R1的触发是有效激活树突状细胞所必需的，而树突状细胞又是诱导自身反应性CD4+T细胞和自身免疫的先决条件。
Dilated cardiomyopathy, resulting from myocarditis, is the most common cause of heart failure in young patients. We here show that interleukin (IL)-1 receptor type 1–deficient (IL-1R1−/−) mice are protected from development of autoimmune myocarditis after immunization with α-myosin-peptide(614–629). CD4+ T cells from immunized IL-1R1−/− mice proliferated poorly and failed to transfer disease after injection into naive severe combined immunodeficiency (SCID) mice. In vitro stimulation experiments suggested that the function of IL-1R1−/−CD4+ T cells was not intrinsically defect, but their activation by dendritic cells was impaired in IL-1R1−/− mice. Accordingly, production of tumor necrosis factor (TNF)-α, IL-1, IL-6, and IL-12p70 was reduced in dendritic cells lacking the IL-1 receptor type 1. In fact, injection of immature, antigen-loaded IL-1R1+/+ but not IL-1R1−/− dendritic cells into IL-1R1−/− mice fully restored disease susceptibility by rendering IL-1R1−/− CD4+ T cells pathogenic. Thus, IL-1R1 triggering is required for efficient activation of dendritic cells, which is in turn a prerequisite for induction of autoreactive CD4+ T cells and autoimmunity.
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DOI：
10.1016/s0167-5699(00)01611-x
发表时间：
2000-05-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
O'Neill, LAJ;Dinarello, CA
通讯作者：
Dinarello, CA
影响因子：
4.4
作者：
al-Ramadi, BK;Welte, T;Bothwell, ALM
通讯作者：
Bothwell, ALM
DOI：
10.1084/jem.178.5.1837
发表时间：
1993-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Penninger JM;Neu N;Timms E;Wallace VA;Koh DR;Kishihara K;Pummerer C;Mak TW
通讯作者：
Mak TW
影响因子：
15.3
作者：
Menges, Mauritius;Rossner, Susanne;Voigtlander, Constanze;Schindler, Heike;Kukutsch, Nicole A;Bogdan, Christian;Erb, Klaus;Schuler, Gerold;Lutz, Manfred B
通讯作者：
Lutz, Manfred B
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G