Mesenchymal stem cells (MSCs) can modulate dendritic cells (DCs) activation and induce tolerogenic characteristics in DCs. All mechanisms involved in MSCs-induced tolerogenic DCs are not fully understood. MicroRNAs (miRs) play important role in maturation and function of DCs. In this study, we investigated the effects of MSCs culture supernatant (C.S.) on expression of miR-155 and miR-23b in mice DCs. BALB/c mice spleens were used for DCs isolation. MSCs were isolated from the mice bone marrow and cultured in DMEM media. When MSCs expanded to sixth passage, C.S. was collected after 12, 24 and 48 h. Quantitative polymerase chain reaction (QPCR) was used to determine the expression of miR-155 and miR-23b in DCs treated with C.S. after 6 and 12 h. Secretion of IL-23 and TGF- β were detected in DCs treated with C.S. by ELISA after 24 h. miR-23b expression was significantly increased in DCs treated with 12 h C.S. for 12 h compared to negative controls. miR-155 expression did not change in DCs treated with C.S. after 6 and 12 h. miR-23b expression was significantly increased in DCs treated with 12 h C.S. for 12 h, compared to those treated with C.S. for 6 h. Similarly, miR-23b expression was increased in DCs treated with 24 h C.S. for 12 h when compared to those treated for 6 h. Production of TGF-β and IL-23 were not influenced by C.S. In conclusion, miR-23b is considered to be one of the mechanisms involved in tolerogenic DCs induction by C.S. in a time-dependent manner.

The presence of natural auto-antibodies (NAbs) in normal range/activity in healthy individuals is essential for body to maintain hemostasis, which are directed to self and altered self-components, while abnormal activity of this system can be associated with several health related diseases. It has been shown that NAbs regulate immune system, and can be changed during the individual's life. In other word, the level and pattern of Nabs is among the main factors to define the state of the body, suggesting their prognostic values as markers of immune system impairment such as autoimmunity and cancer. Such NAbs have gained substantial attention because several of them, including their recombinant forms, have therapeutic potential (e.g., programmed cell death-1 [PD-1, Pdcd1], which some of its inhibitors have been approved by FDA for cancer therapy). Whereas a large number of IgM and IgG NAbs have a key role in tissue homeostasis, while others modulate cellular and enzyme properties. The aim of current review is to give an overview about some of these NAbs and how these low-titer/affinity interact with Ag in homeostasis, with particular emphasis on related diseases such as systemic inflammatory response syndrome and cancer, and their application as potential therapeutic target for cancer therapy.

BackgroundCichorium intybus is a medicinal plant commonly used in traditional medicine for its benefits in immune-madiated disorders. There are several evidences showing that C. intybus can modulate immune responses. In the present study we have investigated the effects of the ethanolic root extract of this plant on the immune system by targeting dendritic cells (DCs). For this purpose, phenotypic and functional maturity of murine DCs after treatment with the extract was analyzed by flow cytometry and mixed lymphocyte reaction (MLR) assay.ResultsC. intybus did not change the expression of CD40, CD86 and MHC-II molecules as important co-stimulatory markers on DCs compared to the control, indicating that it could not promote DCs phenotypic maturation. Treatment of DCs with lower concentrations of the extract resulted in an increased production of IL-12 by these cells with no change in IL-10 release. The capacity of treated DCs to stimulate allogenic T cells proliferation and cytokines secretion was examined in the co-cuture of these cells with T cells in MLR. C. intybus at higher concentrations inhibited proliferation of allogenic T cells and in lower concentrations changed the level of cytokines such that IL-4 decreased and IFN-γ increased.ConclusionsThese results indicated that C. intybus extract at higher concentrations can inhibit T cell stimulating activity of DCs, whereas at lower concentrations can modulate cytokine secretion toward a Th1 pattern. These data may in part explain the traditional use of this plant in treatment of immune-mediated disorders.

This study demonstrated the capability of L. infantum-derived rHSP70 in maturating BALB/c mice splenic DCs and in vivo polarization of immunity to a Th1 response.

Taken together, these data demonstrate that downregulation of CD40 in DCs can expand Treg cells and increase skin allograft survival.