VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene expression in response to simulated immune complexes.
VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene expression in response to simulated immune complexes.
复制标题
DOI：
10.1186/s13075-017-1474-y
复制
发表时间：
2017-12-08
影响因子：
4.9
通讯作者：
Fava RA
中科院分区：
文献类型：
--
作者：
Ceeraz S;Eszterhas SK;Sergent PA;Armstrong DA;Ashare A;Broughton T;Wang L;Pechenick D;Burns CM;Noelle RJ;Vincenti MP;Fava RA
除了活化的T细胞之外，免疫检查点抑制剂“T细胞活化的含V结构域的IG抑制剂”（VISTA）由骨髓细胞类型（包括巨噬细胞和嗜中性粒细胞）表达。评估了骨髓细胞表达VISTA对抗体诱导的关节炎的重要性及其在人类疾病中的相关性潜力。将VISTA免疫定位在正常和关节炎人滑膜组织切片中，并对滑膜组织裂解物进行蛋白质印迹分析。用针对VISTA的抗体处理的DBA/1 J小鼠和VISTA缺陷小鼠（V-KO）进行胶原抗体诱导的关节炎模型（CAIA）。用NanoString阵列分析来自关节炎关节、脾脏和培养的巨噬细胞的总mRNA。测定脾脏炎性巨噬细胞分泌的细胞因子。用培养的巨噬细胞进行体外趋化性和信号转导测定。VISTA蛋白定位于滑膜细胞、中性粒细胞和富含淋巴细胞的病灶中的分散细胞，并通过蛋白质印迹分析在正常滑膜和类风湿性关节炎患者的滑膜中检测到。VISTA缺乏或用抗VISTA单克隆抗体处理小鼠减弱CAIA。V-KO小鼠的关节损伤和MMP-3表达显著降低。在来自V-KO的单核细胞、嗜中性粒细胞和培养的巨噬细胞上，C5 a受体的表面表达减少。在体外Fc受体结合后，与WT相比，V-KO巨噬细胞的基因表达发生了深刻变化，包括IL-1受体拮抗剂（IL 1 rn）的显著诱导。VISTA表达支持CAIA中的免疫复合物炎症，并且VISTA在人滑膜中表达。VISTA支持对C5 a的最佳应答并调节巨噬细胞对免疫复合物的应答。本文的在线版本（doi：10.1186/s13075-017-1474-y）包含补充材料，可供授权用户使用。
In addition to activated T cells, the immune checkpoint inhibitor “V domain-containing Ig suppressor of T-cell activation” (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated. VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis. The collagen antibody-induced arthritis model (CAIA) was performed with DBA/1 J mice treated with antibodies against VISTA and with VISTA-deficient mice (V-KO). Total mRNA from arthritic joints, spleens, and cultured macrophages was analyzed with NanoString arrays. Cytokines secreted by splenic inflammatory macrophages were determined. In-vitro chemotaxis and signal transduction assays were performed with cultured macrophages. VISTA protein was localized to synovial membrane cells, neutrophils, and scattered cells in lymphocyte-rich foci and was detected by western blot analysis in normal synovium and synovium from rheumatoid arthritis patients. Deficiency of VISTA or treatment of mice with anti-VISTA monoclonal antibodies attenuated CAIA. Joint damage and MMP-3 expression were significantly reduced in V-KO mice. Surface expression of C5a receptor was reduced on monocytes, neutrophils, and cultured macrophages from V-KO. Upon Fc receptor engagement in vitro, gene expression by V-KO macrophages was altered profoundly compared to WT, including a significant induction of IL-1 receptor antagonist (IL1rn). VISTA expression supports immune-complex inflammation in CAIA and VISTA is expressed in human synovium. VISTA supports optimal responses to C5a and modulates macrophage responses to immune complexes. The online version of this article (doi:10.1186/s13075-017-1474-y) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
11.2
作者：
Le Mercier I;Chen W;Lines JL;Day M;Li J;Sergent P;Noelle RJ;Wang L
通讯作者：
Wang L
DOI：
10.4049/jimmunol.1102310
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banda NK;Hyatt S;Antonioli AH;White JT;Glogowska M;Takahashi K;Merkel TJ;Stahl GL;Mueller-Ortiz S;Wetsel R;Arend WP;Holers VM
通讯作者：
Holers VM
影响因子：
4.9
作者：
Asnagli H;Martire D;Belmonte N;Quentin J;Bastian H;Boucard-Jourdin M;Fall PB;Mausset-Bonnefont AL;Mantello-Moreau A;Rouquier S;Marchetti I;Jorgensen C;Foussat A;Louis-Plence P
通讯作者：
Louis-Plence P
DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
82.9
作者：
Gao J;Ward JF;Pettaway CA;Shi LZ;Subudhi SK;Vence LM;Zhao H;Chen J;Chen H;Efstathiou E;Troncoso P;Allison JP;Logothetis CJ;Wistuba II;Sepulveda MA;Sun J;Wargo J;Blando J;Sharma P
通讯作者：
Sharma P