Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Front Immunol. 2022 Aug 11;13:943574. doi: 10.3389/fimmu.2022.943574. eCollection 2022.
Although polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on studies in blood. We investigated T helper 1 (T) and T helper 17 (T) cell responses in blood, synovial fluid and bursa tissue of patients with PMR.
Blood samples were collected from 18 patients with new-onset PMR and 32 healthy controls. Synovial fluid was aspirated from the inflamed shoulder bursae or biceps tendon sheath of 13 patients. Ultrasound-guided biopsies of the subacromial-subdeltoid (SASD) bursa were obtained from 11 patients. T cells were examined by flow cytometry, immunohistochemistry and immunofluorescence staining.
Besides an increase of T (CD4IL-17IFN-γ) cells and T cytotoxic 17 (T; CD8IL-17IFN-γ) cells, no other major changes were noted in the circulating T cell compartment of patients with PMR. Absolute numbers of CD4 and CD8 T cells were similar in blood and synovial fluid of patients with PMR. Synovial fluid T cells showed an effector-memory (CD45ROCCR7) phenotype. Percentages of T (CD4IFN-γIL-17) cells and T/T (CD4IFN-γIL-17) cells, but not T or T cells, were increased in the synovial fluid. Bursa tissue biopsies contained a small number of T cells, which were mostly CD8 negative. The majority of bursa tissue T cells produced IFN-γ but not IL-17. For comparison, B cells were scarcely detected in the bursa tissue.
Although the circulating T cell pool is expanded in patients with PMR, our findings indicate that T cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the T cell pathway as a potential target for therapy in PMR.
尽管巨细胞动脉炎（PMR）是一种非常常见的风湿性炎症性疾病，但目前对 PMR 的病理生物学的了解有限，且主要基于血液研究。我们研究了初诊 PMR 患者血液、滑液和滑囊组织中的辅助性 T 细胞 1（Th1）和 Th17 细胞反应。
采集了 18 例新发 PMR 患者和 32 例健康对照者的血液样本。13 例患者的炎症性肩滑囊或肱二头肌腱鞘抽吸滑液。11 例患者经超声引导进行肩峰下-三角肌下滑囊活检。采用流式细胞术、免疫组化和免疫荧光染色检测 T 细胞。
除了 Th1（CD4IL-17IFN-γ）细胞和 Th17 细胞毒性（T；CD8IL-17IFN-γ）细胞增加外，PMR 患者循环 T 细胞群没有其他明显变化。PMR 患者血液和滑液中的 CD4 和 CD8 T 细胞绝对数相似。滑液 T 细胞表现为效应记忆表型（CD45ROCCR7）。Th1（CD4IFN-γIL-17）细胞和 Th1/T（CD4IFN-γIL-17）细胞的比例，而不是 Th1 或 Th17 细胞，在滑液中增加。滑囊组织活检包含少量 T 细胞，这些细胞大多为 CD8 阴性。大多数滑囊组织 T 细胞产生 IFN-γ，但不产生 IL-17。相比之下，B 细胞在滑囊组织中很少被检测到。
尽管 PMR 患者的循环 T 细胞池扩大，但我们的研究结果表明，T 细胞参与了这种情况下的滑囊和腱鞘炎症。我们的研究表明 T 细胞途径可能是 PMR 治疗的潜在靶点。
