Anti-ICOSL New Antigen Receptor Domains Inhibit T Cell Proliferation and Reduce the Development of Inflammation in the Collagen-Induced Mouse Model of Rheumatoid Arthritis.
Anti-ICOSL New Antigen Receptor Domains Inhibit T Cell Proliferation and Reduce the Development of Inflammation in the Collagen-Induced Mouse Model of Rheumatoid Arthritis.
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DOI：
10.1155/2018/4089459
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发表时间：
2018
影响因子：
4.1
通讯作者：
Barelle CJ
中科院分区：
文献类型：
--
作者：
O'Dwyer R;Kovaleva M;Zhang J;Steven J;Cummins E;Luxenberg D;Darmanin-Sheehan A;Carvalho MF;Whitters M;Saunders K;Barelle CJ
淋巴细胞共刺激在免疫学、炎症和免疫治疗中起着核心作用。诱导型T细胞共刺激分子（ICOS）在肽：MHC与CD 28共刺激接合后在T细胞上表达。ICOS与其唯一配体诱导型T细胞共刺激配体（ICOSL;也称为B7相关蛋白-1）的相互作用触发T细胞的许多关键活性，包括分化和细胞因子产生。T细胞活化的抑制可以通过阻断这种相互作用来实现，并且已经显示出在自身免疫模型中是改善疾病的有效手段。在这项研究中，我们从合成的噬菌体展示库中分离出特异性抗ICOSL新抗原受体结构域，并证明它们能够阻断ICOS/ICOSL相互作用并抑制T细胞增殖。在类风湿性关节炎的胶原蛋白诱导的小鼠模型中测试抗小鼠ICOSL结构域（在此被认为是在患者治疗中使用抗人ICOSL结构域的替代物）的功效，其中它们显著降低关节炎症并延迟和降低总体疾病进展和严重程度。
Lymphocyte costimulation plays a central role in immunology, inflammation, and immunotherapy. The inducible T cell costimulator (ICOS) is expressed on T cells following peptide: MHC engagement with CD28 costimulation. The interaction of ICOS with its sole ligand, the inducible T cell costimulatory ligand (ICOSL; also known as B7-related protein-1), triggers a number of key activities of T cells including differentiation and cytokine production. Suppression of T cell activation can be achieved by blocking this interaction and has been shown to be an effective means of ameliorating disease in models of autoimmunity. In this study, we isolated specific anti-ICOSL new antigen receptor domains from a synthetic phage display library and demonstrated their ability to block the ICOS/ICOSL interaction and inhibit T cell proliferation. Anti-mouse ICOSL domains, considered here as surrogates for the use of anti-human ICOSL domains in patient therapy, were tested for efficacy in a collagen-induced mouse model of rheumatoid arthritis where they significantly decreased the inflammation of joints and delayed and reduced overall disease progression and severity.
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DOI：
10.1002/art.40479
发表时间：
2018-07
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Cheng LE;Amoura Z;Cheah B;Hiepe F;Sullivan BA;Zhou L;Arnold GE;Tsuji WH;Merrill JT;Chung JB
通讯作者：
Chung JB
影响因子：
7.3
作者：
Kovaleva M;Johnson K;Steven J;Barelle CJ;Porter A
通讯作者：
Porter A
影响因子：
4.7
作者：
Griffiths, Katherine;Dolezal, Olan;Foley, Michael
通讯作者：
Foley, Michael
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.
影响因子：
6.8
作者：
Bourne, Tim;Fossati, Gianluca;Nesbitt, Andrew
通讯作者：
Nesbitt, Andrew