Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice.
Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice.
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DOI：
10.4049/jimmunol.181.8.5264
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发表时间：
2008-10-15
期刊：
影响因子：
--
通讯作者：
Yamamoto K
中科院分区：
文献类型：
--
作者：
Okamoto A;Fujio K;van Rooijen N;Tsuno NH;Takahashi K;Tsurui H;Hirose S;Elkon KB;Yamamoto K
自身抗原呈递给T细胞对于自身免疫性疾病的发展至关重要。然而，自身抗原呈递的机制知之甚少。在这项研究中，我们表明，脾吞噬细胞在自身抗原呈递在小鼠狼疮中发挥重要作用。核小体是系统性红斑狼疮的主要自身抗原。我们发现，与淋巴结、肺和胸腺相比，核小体特异性T细胞主要在脾脏中被刺激。在脾脏APC中，F4/80+巨噬细胞和CD 11b + CD 11 c+树突状细胞是核小体特异性T细胞的强刺激因子。当（NZB × NZW）F1（NZB/W F1）小鼠脾脏吞噬细胞被耗尽时，脾脏中核小体的呈递被显著抑制。此外，脾吞噬细胞的耗竭显着抑制抗核小体抗体和抗双链DNA抗体的生产。吞噬细胞耗竭小鼠蛋白尿进展延迟，生存期延长。吞噬细胞耗竭小鼠脾脏中自身抗体分泌细胞的数量减少。多次注射脾F4/80+巨噬细胞，而不是脾CD 11 c+树突状细胞，诱导NZB/WF 1小鼠产生自身抗体和蛋白尿进展。这些结果表明，自身抗原呈递脾吞噬细胞，包括巨噬细胞显着有助于自身抗体的产生和狼疮易感小鼠的疾病进展。
Autoantigen presentation to T cells is crucial for the development of autoimmune disease. However, the mechanisms of autoantigen presentation are poorly understood. In this study, we show that splenic phagocytes play an important role in autoantigen presentation in murine lupus. Nucleosomes are major autoantigens in systemic lupus erythematosus. We found that nucleosome-specific T cells were stimulated dominantly in the spleen, compared with lymph nodes, lung, and thymus. Among splenic APCs, F4/80+macrophages and CD11b+CD11c+ dendritic cells were strong stimulators for nucleosome-specific T cells. When splenic phagocytes were depleted in (NZB × NZW) F1 (NZB/W F1) mice, nucleosome presentation in the spleen was dramatically suppressed. Moreover, depletion of splenic phagocytes significantly suppressed anti-nucleosome Ab and anti-dsDNA Ab production. Proteinuria progression was delayed and survival was prolonged in phagocyte-depleted mice. The numbers of autoantibody-secreting cells were decreased in the spleen from phagocyte-depleted mice. Multiple injections of splenic F4/80+ macrophages, not those of splenic CD11c+ dendritic cells, induced autoantibody production and proteinuria progression in NZB/W F1 mice. These results indicate that autoantigen presentation by splenic phagocytes including macrophages significantly contributes to autoantibody production and disease progression in lupus-prone mice.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
--
作者：
Muraoka, Masatake;Hasegawa, Hitoshi;Yasukawa, Masaki
通讯作者：
Yasukawa, Masaki
影响因子：
--
作者：
AMOURA, Z;CHABRE, H;JACOB, L
通讯作者：
JACOB, L
淋巴细胞进入脾白髓的整合素依赖性。
DOI：
10.1084/jem.20021569
发表时间：
2003-02-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lo CG;Lu TT;Cyster JG
通讯作者：
Cyster JG
影响因子：
4.4
作者：
Radic, M;Marion, T;Monestier, M
通讯作者：
Monestier, M