Suppression of allograft rejection by regulatory B cells induced via TLR signaling.
Suppression of allograft rejection by regulatory B cells induced via TLR signaling.
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DOI：
10.1172/jci.insight.152213
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发表时间：
2022-09-08
期刊：
影响因子：
8
通讯作者：
Markmann, James F.
中科院分区：
文献类型：
--
作者：
Lee, Kang Mi;Fu, Qiang;Huai, Guoli;Deng, Kevin;Lei, Ji;Kojima, Lisa;Agarwal, Divyansh;van Galen, Peter;Kimura, Shoko;Tanimine, Naoki;Washburn, Laura;Yeh, Heidi;Naji, Ali;Rickert, Charles G.;LeGuern, Christian;Markmann, James F.
B淋巴细胞对于获得性免疫的关键贡献早已被认识到，其通过同源抗原呈递给T细胞和Ab产生来提供针对病原体的防御。最近认识到，B细胞在确保自身耐受性中也是不可或缺的;这引起了人们对它们用于下调不需要的免疫应答（例如移植排斥）的治疗应用的兴趣。在这项研究中，我们发现，PMA和离子霉素激活的小鼠B细胞获得的调节特性后，通过TLR 4/TLR 9受体（Bregs-TLR）的刺激。Bregs-TLR在体外能有效抑制T细胞增殖，预防同种异体移植排斥反应。与大多数报道的布雷格活性不同，Bregs-TLR对同种免疫应答的抑制依赖于TGF-β而不是IL-10的表达。在体内，Bregs-TLR中断供体特异性T细胞扩增并以TGF-β依赖性方式诱导TcB。RNA-Seq分析证实了TGF-β通路参与Breg-TLR功能，鉴定了与预防移植排斥有关的潜在基因通路，并提出了促进布雷格调节的靶点。
B lymphocytes have long been recognized for their critical contributions to adaptive immunity, providing defense against pathogens through cognate antigen presentation to T cells and Ab production. More recently appreciated is that B cells are also integral in securing self-tolerance; this has led to interest in their therapeutic application to downregulate unwanted immune responses, such as transplant rejection. In this study, we found that PMA- and ionomycin-activated mouse B cells acquire regulatory properties following stimulation through TLR4/TLR9 receptors (Bregs-TLR). Bregs-TLR efficiently inhibited T cell proliferation in vitro and prevented allograft rejection. Unlike most reported Breg activities, the inhibition of alloimmune responses by Bregs-TLR relied on the expression of TGF-β and not IL-10. In vivo, Bregs-TLR interrupted donor-specific T cell expansion and induced Tregs in a TGF-β–dependent manner. RNA-Seq analyses corroborated the involvement of TGF-β pathways in Breg-TLR function, identified potential gene pathways implicated in preventing graft rejection, and suggested targets to foster Breg regulation.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
1.5
作者：
Azhar, Mohamad;Yin, Moying;Bommireddy, Ramireddy;Duffy, John J.;Yang, Junqi;Pawlowski, Sharon A.;Boivin, Gregory P.;Engle, Sandra J.;Sanford, L. P.;Grisham, Christina;Singh, Ram R.;Babcock, George F.;Doetschman, Thomas
通讯作者：
Doetschman, Thomas
影响因子：
24.8
作者：
Marino, Jose;Babiker-Mohamed, Mohamed H.;Benichou, Gilles
通讯作者：
Benichou, Gilles
影响因子：
4.4
作者：
Deng, Shaoping;Moore, Daniel J.;Markmann, James F.
通讯作者：
Markmann, James F.
DOI：
10.4049/jimmunol.2000612
发表时间：
2020-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jones DM;Read KA;Oestreich KJ
通讯作者：
Oestreich KJ