Abstract 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.