Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice.
Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice.
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DOI：
10.1371/journal.pone.0010558
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发表时间：
2010-05-10
期刊：
影响因子：
3.7
通讯作者：
Graca L
中科院分区：
文献类型：
--
作者：
Duarte J;Agua-Doce A;Oliveira VG;Fonseca JE;Graca L
类风湿性关节炎（RA）是一种慢性免疫介导的疾病，与许多细胞类型的失调有关。据报道，不同的T细胞亚群在疾病发病机制中具有相反的作用，特别是Th 17和Treg细胞。我们研究了非消耗性抗CD 4单克隆抗体是否可以通过影响Th 17/Treg平衡来保护SKG小鼠（最近描述的RA动物模型）免受慢性自身免疫性关节炎的影响。我们发现，非消耗性抗CD 4可预防SKG小鼠慢性自身免疫性关节炎的发作。此外，经治疗的小鼠在抗CD 4治疗后长达60天内免受关节炎的诱导，同时仍然能够对无关抗原产生CD 4依赖性免疫应答。抗体治疗也阻止了关节炎小鼠的疾病进展，尽管没有导致缓解。关节炎的保护与Foxp 3的比例增加和滑膜中产生IL-17的T细胞减少有关。在Th 17极化条件下的体外测定显示，CD 4阻断阻止Th 17极化，同时有利于Foxp 3诱导。因此，非消耗性抗CD 4可以通过外周组织中Treg和Th 17细胞频率的相互变化，诱导SKG小鼠免受慢性自身免疫性关节炎的长期保护，从而将平衡转向免疫耐受。
Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells. We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice – a recently described animal model of RA – by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction. Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.
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DOI：
10.1073/pnas.0400084101
发表时间：
2004-07-06
影响因子：
11.1
作者：
Graca, L;Le Moine, A;Waldmann, H
通讯作者：
Waldmann, H
影响因子：
--
作者：
Gabriel, SE;Crowson, CS;Matteson, EL
通讯作者：
Matteson, EL
影响因子：
4.4
作者：
Cobbold, SP;Castejon, R;Waldmann, H
通讯作者：
Waldmann, H
影响因子：
4.3
作者：
BREEDVELD, FC;DYNESIUSTRENTHAM, R;TRENTHAM, DE
通讯作者：
TRENTHAM, DE
DOI：
10.1016/0090-1229(91)90084-n
发表时间：
1991-04-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
HORNEFF, G;WINKLER, T;BURMESTER, GR
通讯作者：
BURMESTER, GR