Division of Rheumatology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Laboratorio de Lipides (LIM-10), Hospital das Clinicas (HCFMUSP) da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
PLoS One. 2024 Oct 8;19(10):e0311263. doi: 10.1371/journal.pone.0311263. eCollection 2024.
We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 μg/300 μL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 μL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.
我们假设,在滑膜损伤后,胶原 V(Col V)暴露隐匿抗原,从而产生 Col V 自身抗体,表明对这种分子的免疫耐受丧失,从而导致实验性关节炎中间充质来源的细胞和细胞外基质受损。因此,本研究探讨了在 mBSA/CFA 诱导性关节炎炎症发展后,口服 Col V 对滑膜的影响。在关节内给予 mBSA14 天后,10 只雄性 Lewis 大鼠口服 Col V(500μg/300μL),溶于 0.01N 醋酸(IA-Col V 组)。关节炎组(IA 组,n=10)仅接受关节内 mBSA。对照组(CT-Col V,n=5)给予关节内生理盐水注射(20μL)。IA 组表现出受损的滑膜,细胞浸润导致细胞外基质扩张,特征为 T 和 B 淋巴细胞以及成纤维细胞浸润。相比之下,在 Col V 口服免疫治疗后,IA-Col V 组滑膜炎症明显减轻,IL-10+和 FoxP3+细胞表达强烈,Col V 减少,Col I 增加。此外,与 IA 组相比,IA-Col V 组脾细胞经 Col V 体外刺激后 IL-10 产生增加。各组之间的 PET 成像没有差异。在大鼠 mBSA/CFA 诱导性关节炎中,口服 Col V 治疗可防止炎症和减少滑膜组织损伤,通过调节滑膜基质,显示出抑制滑膜炎的免疫治疗潜力。