Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States.
Department of Pharmaceutics, Zagazig University, Zagazig, Egypt.
Front Immunol. 2022 Jul 4;13:914468. doi: 10.3389/fimmu.2022.914468. eCollection 2022.
We report a novel model of lupus-associated cardiovascular pathology accelerated by the TLR7 agonist R848 in lupus-prone B6. (TC) mice. R848-treated TC mice but not non-autoimmune C57BL/6 (B6) controls developed microvascular inflammation and myocytolysis with intracellular vacuolization. This histopathology was similar to antibody-mediated rejection after heart transplant, although it did not involve complement. The TC or B6 recipients of serum or splenocytes from R848-treated TC mice developed a reactive cardiomyocyte hypertrophy, which also presents spontaneously in old TC mice as well as in TC. mice that lack B and T cells. Each of these cardiovascular lesions correspond to abnormalities that have been reported in lupus patients. Lymphoid and non-lymphoid immune cells as well as soluble factors contribute to lupus-associated cardiovascular lesions in TC mice, which can now be dissected using this model with and without R848 treatment.
我们报告了一种新的狼疮相关心血管病变模型，该模型由 TLR7 激动剂 R848 在狼疮易感 B6. (TC) 小鼠中加速产生。用 R848 处理的 TC 小鼠而非非自身免疫性 C57BL/6 (B6) 对照小鼠会发生微血管炎症和肌细胞溶解，伴有细胞内空泡化。这种组织病理学类似于心脏移植后的抗体介导排斥反应，但不涉及补体。接受来自 R848 处理的 TC 小鼠的血清或脾细胞的 TC 或 B6 受体小鼠发生反应性心肌细胞肥大，这种肥大也会在老年 TC 小鼠以及缺乏 B 和 T 细胞的 TC 小鼠中自发发生。这些心血管病变都与狼疮患者中报告的异常情况相对应。淋巴细胞和非淋巴细胞免疫细胞以及可溶性因子都会导致 TC 小鼠的狼疮相关心血管病变，现在可以使用该模型（有和没有 R848 治疗）对其进行剖析。
