October 2016 | Volume 7 | Article 415 1 ORIGINAL RESEARCH published: 24 October 2016 doi: 10.3389/fmmu.2016.00415 Frontiers in Immunology | www.frontiersin.org Edited by: Ralf Dressel, University of Göttingen, Germany Reviewed by: Jacques A. Nunes, Centre de Recherche en Cancerologie de Marseille, France Karen Bieback, Heidelberg University, Germany *Correspondence: Alessandro Poggi alessandro.poggi@hsanmartino.it † Present address: Rui C. Pereira, Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego, Genova, Italy Specialty section: This article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in Immunology Received: 05 August 2016 Accepted: 26 September 2016 Published: 24 October 2016 Citation: Pereira RC, Martinelli D, Cancedda R, Gentili C and Poggi A (2016) Human Articular Chondrocytes Regulate Immune Response by Affecting Directly T Cell Proliferation and Indirectly Inhibiting Monocyte Differentiation to Professional Antigen-Presenting Cells. Front. Immunol. 7:415. doi: 10.3389/fmmu.2016.00415 Human Articular Chondrocytes Regulate Immune Response by Affecting Directly T Cell Proliferation and Indirectly Inhibiting Monocyte Differentiation to Professional Antigen-Presenting Cells Rui C. Pereira 1† , Daniela Martinelli 1 , Ranieri Cancedda 1 , Chiara Gentili 1 and Alessandro Poggi 2 * 1 Regenerative Medicine Unit, Department of Experimental Medicine, University of Genova, Genova, Italy, 2 Molecular Oncology and Angiogenesis Unit, Department of Integrated Oncological Therapies, IRCCS AOU San Martino IST, Genova, Italy Autologous chondrocyte implantation is the current gold standard cell therapy for carti- lage lesions. However, in some instances, the heavily compromised health of the patient can either impair or limit the recovery of the autologous chondrocytes and a satisfactory outcome of the implant. Allogeneic human articular chondrocytes (hAC) could be a good alternative, but the possible immunological incompatibility between recipient and hAC donor should be considered. Herein, we report that allogeneic hAC inhibited T lympho- cyte response to antigen-dependent and -independent proliferative stimuli. This effect was maximal when T cells and hAC were in contact and it was not relieved by the addition of exogenous lymphocyte growth factor interleukin (IL)-2. More important, hAC impaired the differentiation of peripheral blood monocytes induced with granulocyte monocyte colony-stimulating factor and IL-4 (Mo) to professional antigen-presenting cells, such as dendritic cells (DC). Indeed, a marked inhibition of the onset of the CD1a expression and an ineffective downregulation of CD14 antigens was observed in Mo–hAC co-cultures. Furthermore, compared to immature or mature DC, Mo from Mo–hAC co-cultures did not trigger an effcacious allo-response. The prostaglandin (PG) E2 present in the Mo–hAC co-culture conditioned media is a putative candidate of the hAC-mediated inhibition of Mo maturation. Altogether, these fndings indicate that allogeneic hAC inhibit, rather than trigger, immune response and strongly suggest that an effcient chondrocyte implantation could be possible also in an allogeneic setting. Keywords: allogenic cells, T lymphocyte, immune response, antigen-presenting cells, dendritic cells, chondrocyte implantation INTRODUCTION Articular cartilage, the joints load-bearing tissue, has limited repair and regeneration capacity (1). Chondrocytes, the only cell type present in articular cartilage comprising only 2–5% of the total cartilage volume, are responsible for regulating the integrity and homeostasis of the tissue by their ability to synthesize the structural components of the extracellular matrix (ECM) (2). Cartilage