Del Rey Manuel J, Faré Regina, Usategui Alicia, Cañete Juan D, Bravo Beatriz, Galindo María, Criado Gabriel, Pablos José L
Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.
Unitat d'Artritis, Servei de Reumatologia, Hospital Clínic de Barcelona, Barcelona, Spain.
Arthritis Res Ther. 2016 Mar 15;18:66. doi: 10.1186/s13075-016-0966-5.
CD271(+) stromal cells (SCs) with multipotent stem cell capacity have been identified in synovial tissues, but their functional significance is unknown. We analyzed the distribution of CD271(+) cells in inflammatory synovial tissues as well as their ex vivo immunomodulatory and inflammatory phenotypes.
CD271 expression was analyzed by immunohistochemistry in synovial tissues and by flow cytometry in primary adherent synovial cell cultures from rheumatoid arthritis (RA), osteoarthritis (OA), and non-inflammatory control tissues. Isolation of CD271(+) synovial SCs was carried out by magnetic cell sorting. Allogeneic T-cell/SC cocultures were performed to analyze the regulatory capacity of these cells on T-cell proliferation and cytokine production. The production of inflammatory mediators was analyzed in cultures of sorted CD271(+)/(-) SCs. The capacity of CD271(+)/(-) SCs to induce inflammatory cell recruitment in vivo was evaluated in subcutaneous implants in immunodeficient mice.
CD271(+) SC were detected in non-inflammatory as well as in arthritic synovial tissues with a specific perivascular distribution. CD271(+) SC density was increased in RA and OA compared with normal synovial tissues. T-cell proliferation and cytokine synthesis were similarly modified by CD271(+) and CD271(-) SCs. Sorted CD271(+) SCs from OA synovial tissues released significantly more interleukin (IL)-6, matrix metalloproteinase (MMP)-1, and MMP-3 than CD271(-) SCs. In immunodeficient mice, implants of CD271(+) SCs induced significantly higher myeloid cell infiltration than CD271(-) SCs.
Our results demonstrate that CD271(+) perivascular SCs expand in RA and OA synovial tissues. CD271(+) cells showed enhanced proinflammatory properties ex vivo and in vivo, whereas immunoregulatory properties were equivalent in CD271(+) and CD271(-) SC.
在滑膜组织中已鉴定出具有多能干细胞能力的CD271(+)基质细胞（SCs），但其功能意义尚不清楚。我们分析了炎症性滑膜组织中CD271(+)细胞的分布及其体外免疫调节和炎症表型。
通过免疫组织化学分析滑膜组织中的CD271表达，并通过流式细胞术分析类风湿性关节炎（RA）、骨关节炎（OA）和非炎症对照组织的原代贴壁滑膜细胞培养物中的CD271表达。通过磁性细胞分选法分离CD271(+)滑膜SCs。进行同种异体T细胞/SC共培养，以分析这些细胞对T细胞增殖和细胞因子产生的调节能力。在分选的CD271(+)/(-)SCs培养物中分析炎症介质的产生。在免疫缺陷小鼠的皮下植入物中评估CD271(+)/(-)SCs在体内诱导炎症细胞募集的能力。
在非炎症性和关节炎性滑膜组织中均检测到CD271(+)SCs，具有特定的血管周围分布。与正常滑膜组织相比，RA和OA中CD271(+)SCs密度增加。CD271(+)和CD271(-)SCs对T细胞增殖和细胞因子合成的影响相似。来自OA滑膜组织的分选CD271(+)SCs释放的白细胞介素（IL）-6、基质金属蛋白酶（MMP）-1和MMP-3明显多于CD271(-)SCs。在免疫缺陷小鼠中，CD271(+)SCs植入物诱导的髓样细胞浸润明显高于CD271(-)SCs。
我们的结果表明CD271(+)血管周围SCs在RA和OA滑膜组织中扩增。CD271(+)细胞在体外和体内均表现出增强的促炎特性，而CD271(+)和CD271(-)SCs的免疫调节特性相当。
