Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice.
Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice.
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DOI：
10.4049/jimmunol.0803052
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发表时间：
2009-03-15
期刊：
影响因子：
--
通讯作者：
Mauri C
中科院分区：
文献类型：
--
作者：
Blair PA;Chavez-Rueda KA;Evans JG;Shlomchik MJ;Eddaoudi A;Isenberg DA;Ehrenstein MR;Mauri C
我们之前报道过il - 10+调节性B细胞，已知在控制自身免疫和炎症性疾病中起重要作用，包含在过渡-2未成熟（T2） B细胞池（T2Bregs）中。促进其富集或增强其抑制活性的治疗策略是非常有吸引力的。在这里，我们报告了激动性抗cd40特异性靶向T2 B细胞，并在短期体外培养中丰富B regs。虽然从狼疮小鼠中分离的未经处理的T2 B细胞的转移不能给患病小鼠提供保护，但体外抗cd40生成的T2 B细胞（T2样bregs）的转移通过il -10依赖机制显着改善肾脏疾病和生存。T2-like-Bregs易在脾内积聚，抑制Th1应答，诱导IL-10+CD4+T细胞分化，并向CD4+T细胞传递调控作用。此外，体内给药激动性抗cd40，目前正在试验治疗癌症，停止和逆转已建立狼疮。综上所述，我们的结果提出了一种新的细胞方法来改善实验性狼疮。
We have previously reported that IL10+ regulatory B cells, known to play an important role in controlling autoimmunity and inflammatory disorders, are contained within the Transitional-2 immature (T2) B cell pool (T2Bregs). Therapeutic strategies facilitating their enrichment or enhancing their suppressive activity are highly attractive. Here we report that agonistic anti-CD40 specifically targets T2 B cells and enriches B regs upon short term in vitro culture. Whilst transfer of unmanipulated T2 B cells, isolated from mice with established lupus, failed to confer protection to diseased mice, transfer of in vitro anti-CD40-generated T2 B cells (T2-like-Bregs) significantly improved renal disease and survival by an IL-10-dependent mechanism. T2-like-Bregs readily accumulated in the spleen after transfer, suppressed Th1 responses, induced the differentiation of IL-10+CD4+T cells and conveyed regulatory effect to CD4+T cells. In addition, in vivo administration of agonistic anti-CD40, currently on trial for the treatment of cancer, halted and reversed established lupus. Taken together our results suggest a novel cellular approach for the amelioration of experimental lupus.
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影响因子：
15.3
作者：
Loder, F;Mutschler, B;Ray, R J;Paige, C J;Sideras, P;Torres, R;Lamers, M C;Carsetti, R
通讯作者：
Carsetti, R
影响因子：
32.4
作者：
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通讯作者：
Bhan, AK
影响因子：
5.5
作者：
Leandro, M. J.;Cooper, N.;Edwards, J. C. W.
通讯作者：
Edwards, J. C. W.
影响因子：
82.9
作者：
Mauri, C;Mars, LT;Londei, M
通讯作者：
Londei, M
影响因子：
15.9
作者：
Hu, Chang-Yun;Rodriguez-Pinto, Daniel;Wen, Li
通讯作者：
Wen, Li