Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity.
Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity.
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树突状细胞的组成型消融会破坏CD4 T细胞的自耐力，并导致自发性致命自身免疫性。
DOI：
10.1084/jem.20082394
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发表时间：
2009-03-16
期刊：
影响因子：
--
通讯作者：
Voehringer D
中科院分区：
文献类型：
--
作者：
Ohnmacht C;Pullner A;King SB;Drexler I;Meier S;Brocker T;Voehringer D
缺乏对自身抗原的免疫耐受性导致自身免疫性疾病。在自身免疫的发病过程中，树突状细胞（dc）被认为是启动逃避耐受诱导的自反应性T细胞的关键。然而，由于树突状细胞也能诱导T细胞耐受，因此尚不清楚在稳态条件下是否需要树突状细胞来预防自身免疫。为了解决这个问题，我们将CD11c-Cre小鼠与表达白喉毒素A （DTA）的小鼠杂交，这些小鼠在ROSA26位点的loxp -侧翼新霉素抗性（neoR）磁带的控制下表达白喉毒素A （DTA）。cre介导的neoR盒移除导致DTA表达和传统dc、浆细胞样dc和朗格汉斯细胞的组成损失。这些dc缺失（ΔDC）小鼠显示CD4单阳性胸腺细胞频率增加，CD4 T细胞浸润外周组织。他们出现了自发性自身免疫，其特征是体重减轻、脾肿大、自身抗体形成、中性粒细胞增多、Th1和Th17细胞数量高，以及炎症性肠病。野生型（WT）小鼠可以用ΔDC小鼠的骨髓（BM）重建病理，而接受ΔDC和WT小鼠骨髓的混合骨髓嵌合体仍然健康。这表明，在稳态条件下，dc在防止致命的自身免疫中起着至关重要的作用。
Lack of immunological tolerance against self-antigens results in autoimmune disorders. During onset of autoimmunity, dendritic cells (DCs) are thought to be critical for priming of self-reactive T cells that have escaped tolerance induction. However, because DCs can also induce T cell tolerance, it remains unclear whether DCs are required under steady-state conditions to prevent autoimmunity. To address this question, we crossed CD11c-Cre mice with mice that express diphtheria toxin A (DTA) under the control of a loxP-flanked neomycin resistance (neoR) cassette from the ROSA26 locus. Cre-mediated removal of the neoR cassette leads to DTA expression and constitutive loss of conventional DCs, plasmacytoid DCs, and Langerhans cells. These DC-depleted (ΔDC) mice showed increased frequencies of CD4 single-positive thymocytes and infiltration of CD4 T cells into peripheral tissues. They developed spontaneous autoimmunity characterized by reduced body weight, splenomegaly, autoantibody formation, neutrophilia, high numbers of Th1 and Th17 cells, and inflammatory bowel disease. Pathology could be induced by reconstitution of wild-type (WT) mice with bone marrow (BM) from ΔDC mice, whereas mixed BM chimeras that received BM from ΔDC and WT mice remained healthy. This demonstrates that DCs play an essential role to protect against fatal autoimmunity under steady-state conditions.
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DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
30.5
作者：
Aschenbrenner, Katharina;D'Cruz, Louise M.;Klein, Ludger
通讯作者：
Klein, Ludger
影响因子：
1.5
作者：
Brockschniedier, Damian;Pechmann, Yvonne;Riethmacher, Dieter
通讯作者：
Riethmacher, Dieter
影响因子：
56.9
作者：
Chen, M;Wang, YH;Wang, J
通讯作者：
Wang, J