Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins nucleic acids and additional active molecules and have been implicated in many physiological and pathological processes over the past decade. effect on immune responses by transporting immuno-modulatory effectors such as transcriptional factors non-coding RNA (Species) and cytokines. In addition stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation differentiation and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions methods of EV purification EV molecular content and functional state of both parental and target cells. However mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review we will discuss how stem cell-derived EVs Darapladib may contribute toward the modulation of the immune response. Collectively stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system. with EVs isolated from cells infected with released cytokines and chemokines that contributed toward the activation of the immune response (Walters et al. 2013 On the other hand macrophages infected with the Leishmania parasite secreted EVs enriched with the Leishmania surface protein gp63 which down-regulated the inflammatory response favoring parasite invasion (Hassani and Olivier 2013 Whereas IIR is usually a nonspecific first line of defense against microbial pathogens and other tissue injuries Air flow is usually a specific response induced after Ag acknowledgement by adaptive immune cells followed by activation Darapladib and clonal growth of immune cells transporting the acknowledged Ag-specific receptors (Schenten and Medzhitov 2011 Zhang et al. 2014 In this setting EVs may take action not only Rabbit Polyclonal to ARRB1. as Ag service providers (since they may transfer bacterial viral and tumoral components to APCs; O’Neill and Quah 2008 Walker et al. 2009 Testa et al. 2010 but also as modulators of direct and indirect Ag presentation. Furthermore this house of EVs to carry Ags from parental cells can allow them to act as reporters of foreign brokers in the organism both for the host immune system as well as from a diagnostic point of view (Yá?ez-Mó et al. 2015 For example tumor-derived EVs carry tumor-Ags which can be taken up and processed by DCs and then cross-presented to tumor-specific cytotoxic T-lymphocytes (CTLs; Wolfers et al. 2001 Andre et al. Darapladib 2002 This has been exhibited for EVs isolated from ascites of tumoral patients as well as other tumoral cell lines (Wolfers et al. 2001 Andre et al. 2002 Morelli et al. 2004 This hypothesis is usually supported by the fact that vaccination of mice Darapladib with tumor peptide-pulsed DC-derived EVs induces a potent CD8+ T cell-mediated anti-tumoral effect (Wolfers et al. 2001 On the basis of these findings it can be speculated that tumor-derived EVs carry tumor-specific Ags and that they could be used to stimulate or inhibit the immune anti-tumoral surveillance (Robbins and Morelli 2014 In this regard ongoing studies are exploring their potential role in the field of anti-tumor vaccination as examined by Kunigelis et al. (Kunigelis and Graner 2015 Furthermore APC-derived EVs can also act as “Ag-presenting vesicles” for T-cell clones (Théry et al. 2002 Muntasell et al. 2007 Nolte-‘t Hoen et al. 2009 however this activity appears to be 10-20 times less efficient to that of corresponding APCs probably due to: the small size vesicle diffusion and limited quantity of MHC molecules per vesicle (Zitvogel et al. 1998 Vincent-Schneider et al. 2002 Qazi et al. 2009 Many recent studies on EVs have focused on the dichotomic effects they have around the immune system (see Figure ?Physique1).1). You will find studies that have reported that EVs are able to promote the immune response by transporting foreign Ags (Bhatnagar and Schorey 2007 Robbins and Morelli 2014 as well as inflammatory cytokines (Pizzirani 2007 Zuccato et al. 2007 and therefore also play a role in mediating chronic inflammatory and autoimmune diseases. For instance EVs derived from synovial fluid of patients with rheumatoid arthritis (RA) have higher levels of TNF-alpha compared to healthy controls (Zhang et al. 2006 Furthermore these EVs are able to delay activated T-cell.