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

Manuel J Del Rey,Gabriel Criado,José L Pablos,María Galindo,Regina Faré,Alicia Usategui,Beatriz Bravo,Juan D Cañete

doi:10.1186/s13075-016-0966-5

Manuel J Del Rey, Gabriel Criado + Show 6 more

Open Access

https://doi.org/10.1186/s13075-016-0966-5

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Abstract

BackgroundCD271+ 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.MethodsCD271 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.ResultsCD271+ 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.ConclusionsOur 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 materialThe online version of this article (doi:10.1186/s13075-016-0966-5) contains supplementary material, which is available to authorized users.

Highlights

CD271+ stromal cells (SCs) with multipotent stem cell capacity have been identified in synovial tissues, but their functional significance is unknown
Immunomodulatory properties of CD271+/CD271− SCs To determine whether synovial CD271+ SCs differentially modulate T-cell effector functions, T cells were stimulated with anti-CD3/anti-CD28 beads in the presence of CD271+ and CD271− cells (1:10 ratio of SCs to T cells)
Both CD271+ and CD271− SCs inhibited the proliferation of allogeneic T cells (Fig. 3a)

Summary

Introduction

CD271+ stromal cells (SCs) with multipotent stem cell capacity have been identified in synovial tissues, but their functional significance is unknown. The mesenchymal or stromal cell lineage in synovial tissue is represented by a heterogeneous population of stromal or fibroblastic cells, usually termed synovial fibroblasts (SFs) or type B synoviocytes. Under normal conditions, these cells contribute to the homeostasis. MSCs are abundant in the bone marrow (BM) as well as in most connective tissues, including synovial tissues [13, 14] Because these cells lack specific markers, their identification in synovial tissues or SF cultures is difficult. Different studies have shown their potential contribution to cartilage repair ex vivo [16, 17, 19], but it is not known whether CD271+ synovial SCs can play immunomodulatory functions in arthritic inflammatory processes

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