Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice.
Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice.
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DOI：
10.1186/ar2122
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发表时间：
2007
影响因子：
4.9
通讯作者：
Yasukawa M
中科院分区：
文献类型：
--
作者：
Hasegawa H;Inoue A;Muraoka M;Yamanouchi J;Miyazaki T;Yasukawa M
CD 4 + CD 25+调节性T细胞的连续转移已显示在自身免疫性疾病的动物模型中具有治疗效果。趋化因子在动物模型和人类自身免疫性疾病的发展中起重要作用。本研究旨在探讨通过在MRL/MpJ-lpr/lpr（MRL/lpr）小鼠的靶器官中有效地积累表达趋化因子受体的CD 4 + CD 25+调节性T细胞是否可以更显著地减少器官特异性自身免疫性疾病的进展。将CD 4 + CD 25 + Foxp 3 + T细胞（Treg细胞）和CD 4 + CD 25 + Foxp 3 + CCR 2转染的T细胞（CCR 2-Treg细胞）经眶后注射到12周龄MRL/lpr小鼠肺炎和涎腺炎早期，并评价其病理变化。单核细胞趋化蛋白-1（MCP-1）/CCL 2在小鼠肺和下颌下腺中的表达呈年龄依赖性增加。CCR 2-Treg细胞的CCR 2表达水平和MCP-1趋化活性明显高于Treg细胞。与接受Treg细胞的MRL/lpr小鼠相比，转移了CCR 2-Treg细胞的MRL/lpr小鼠显示肺炎和涎腺炎的进展显著减少。这是由于CCR 2-Treg细胞更明显的迁移和它们在表达MCP-1的肺和下颌下腺中更长时间的定位，导致更强的抑制活性。我们制备了表达趋化因子受体的Treg细胞，并证明了它们通过在靶器官中积累来改善疾病进展的能力。这种方法可能为靶抗原尚未确定的器官特异性自身免疫性疾病提供一种新的治疗方法。
Adoptive transfer of CD4+CD25+ regulatory T cells has been shown to have therapeutic effects in animal models of autoimmune diseases. Chemokines play an important role in the development of autoimmune diseases in animal models and humans. The present study was performed to investigate whether the progression of organ-specific autoimmune diseases could be reduced more markedly by accumulating chemokine receptor-expressing CD4+CD25+ regulatory T cells efficiently in target organs in MRL/MpJ-lpr/lpr (MRL/lpr) mice. CD4+CD25+Foxp3+ T cells (Treg cells) and CD4+CD25+Foxp3+ CCR2-transfected T cells (CCR2-Treg cells) were transferred via retro-orbital injection into 12-week-old MRL/lpr mice at the early stage of pneumonitis and sialadenitis, and the pathological changes were evaluated. Expression of monocyte chemoattractant protein-1 (MCP-1)/CCL2 was observed in the lung and submandibular gland of the mice and increased age-dependently. The level of CCR2 expression and MCP-1 chemotactic activity of CCR2-Treg cells were much higher than those of Treg cells. MRL/lpr mice to which CCR2-Treg cells had been transferred showed significantly reduced progression of pneumonitis and sialadenitis in comparison with MRL/lpr mice that had received Treg cells. This was due to more pronounced migration of CCR2-Treg cells and their localization for a longer time in MCP-1-expressing lung and submandibular gland, resulting in stronger suppressive activity. We prepared chemokine receptor-expressing Treg cells and demonstrated their ability to ameliorate disease progression by accumulating in target organs. This method may provide a new therapeutic approach for organ-specific autoimmune diseases in which the target antigens remain undefined.
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DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D
影响因子：
4.4
作者：
Misra, N;Bayry, J;Kaveri, SV
通讯作者：
Kaveri, SV
影响因子：
--
作者：
Hasegawa, H;Kohno, M;Fujita, S
通讯作者：
Fujita, S
影响因子：
56.9
作者：
Hori, S;Nomura, T;Sakaguchi, S
通讯作者：
Sakaguchi, S
影响因子：
30.5
作者：
Gavin, MA;Clarke, SR;Rudensky, A
通讯作者：
Rudensky, A