CD271(+) stromal cells expand in arthritic synovium and exhibit a proinflammatory phenotype

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-016-0966-5) contains supplementary material, which is available to authorized users.