Attenuation of Murine Collagen-Induced Arthritis by Targeting CD6.
Attenuation of Murine Collagen-Induced Arthritis by Targeting CD6.
复制标题
通过靶向CD6，鼠胶原蛋白诱导的关节炎的衰减。
DOI：
10.1002/art.41288
复制
发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Li Y;Ruth JH;Rasmussen SM;Athukorala KS;Weber DP;Amin MA;Campbell PL;Singer NG;Fox DA;Lin F
CD6是T细胞功能的重要调节因子，可与配体CD166和CD318相互作用。为了进一步阐明CD6在类风湿关节炎（RA）中的意义，我们使用CD6敲除（KO）小鼠和CD6人源化小鼠，在其T细胞上表达人CD6而不是小鼠CD6，研究了靶向CD6在小鼠胶原诱导关节炎（CIA）模型中的作用。我们用胶原乳剂免疫野生型（Wt）和CD6基因KO小鼠诱导CIA。在使用人源化CD6小鼠的治疗研究中，同样对小鼠进行免疫，并在第7、14和21天注射UMCD6（小鼠抗人CD6 IgG）或对照IgG。评估关节组织的组织损伤、白细胞浸润和局部炎症细胞因子的产生。在CIA Wt和CD6 KO小鼠中，还评估了胶原特异性Th1、Th9和Th17反应和血清中胶原特异性IgG亚类的水平。缺乏CD6可降低1)胶原特异性Th9和Th17，但不降低Th1反应；2)许多促炎关节细胞因子；3)血清中胶原反应性总IgG和IgG1水平，但不降低IgG2a和IgG3水平。与Wt小鼠相比，CIA CD6 KO的关节匀浆血红蛋白（Hb）含量显著降低（血管生成减少）。此外，用小鼠抗人CD6单克隆抗体（mAb）治疗CD6人源化小鼠在减少CIA关节炎症方面同样有效。综上所述，这些数据表明CD6与其配体的相互作用对于CIA和其他由T细胞驱动的炎性关节炎的延续是重要的。
CD6 is an important regulator of T cell function that interacts with the ligands CD166 and CD318. To further clarify the significance of CD6 in rheumatoid arthritis (RA), we examined the effects of targeting CD6 in the mouse collagen-induced arthritis (CIA) model, using CD6 knockout (KO) mice and CD6 humanized mice that express human CD6 in lieu of mouse CD6 on their T cells. We immunized wild type (Wt) and CD6 gene KO mice with a collagen emulsion to induce CIA. For treatment studies using humanized CD6 mice, mice were immunized similarly and UMCD6 (a mouse anti-human CD6 IgG) or control IgG was injected on days 7, 14, and 21. Joint tissues were evaluated for tissue damage, leukocyte infiltration, and local inflammatory cytokine production. Collagen-specific Th1, Th9 and Th17 responses and serum levels of collagen-specific IgG subclasses were also evaluated in CIA Wt and CD6 KO mice. Absence of CD6 reduced 1) collagen-specific Th9 and Th17, but not Th1 responses, 2) many pro-inflammatory joint cytokines, 3) serum levels of collagen-reactive total IgG and IgG1, but not IgG2a and IgG3. Joint homogenate hemoglobin (Hb) content was significantly reduced in CIA CD6 KO compared to Wt mice (reduced angiogenesis). Moreover, treating CD6 humanized mice with mouse anti-human CD6 monoclonal antibody (mAb) was similarly effective in reducing joint inflammation in CIA. Taken together, these data suggest that interaction of CD6 with its ligands is important for perpetuation of CIA and other inflammatory arthritides that are T cell driven.
登录
查看更多内容
影响因子：
--
作者：
Isozaki, Takeo;Arbab, Ali S.;Haas, Christian S.;Amin, M. Asif;Arendt, Monica D.;Koch, Alisa E.;Ruth, Jeffrey H.
通讯作者：
Ruth, Jeffrey H.
影响因子：
4.3
作者：
OSORIO, LM;ORDONEZ, C;CHOW, SC
通讯作者：
CHOW, SC
DOI：
10.1084/jem.20151785
发表时间：
2016-07-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Orta-Mascaró M;Consuegra-Fernández M;Carreras E;Roncagalli R;Carreras-Sureda A;Alvarez P;Girard L;Simões I;Martínez-Florensa M;Aranda F;Merino R;Martínez VG;Vicente R;Merino J;Sarukhan A;Malissen M;Malissen B;Lozano F
通讯作者：
Lozano F
缺乏内皮选择素的小鼠中关节炎的加速发育。
影响因子：
4.9
作者：
Ruth JH;Amin MA;Woods JM;He X;Samuel S;Yi N;Haas CS;Koch AE;Bullard DC
通讯作者：
Bullard DC
DOI：
10.1084/jem.181.6.2213
发表时间：
1995-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bowen MA;Patel DD;Li X;Modrell B;Malacko AR;Wang WC;Marquardt H;Neubauer M;Pesando JM;Francke U
通讯作者：
Francke U