Search

Introduction: Restoring immune tolerance is a promising area of therapy for autoimmune diseases. One method that helps restore immunological tolerance is the approach using tolerogenic dendritic cells (tolDCs). In our study, we analyzed the effectiveness of using dendritic cells transfected with DNA constructs encoding IL-10, type II collagen, and CCR9 to induce immune tolerance in an experimental model of arthritis. Methods: Dendritic cell cultures were obtained from bone marrow cells of Balb/c mice. Dendritic cells (DCs) cultures were transfected with pmaxCCR9, pmaxIL-10, and pmaxCollagen type II by electroporation. The phenotype and functions of DCs were studied using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Migration of electroporated DCs was assessed in vitro. Induction of antigen-collagen induced arthritis (ACIA) was carried out according to the protocol in Balb/c mice. DCs were then administered to ACIA mice. The development of arthritis was monitored by measuring paw swelling with a caliper at different time points. The immunological changes were assessed by analyzing the content of antibodies to type II collagen using enzyme immunoassay. Additionally, a histological examination of the joint tissue was conducted, followed by data analysis. The results are as follows: DCs were obtained, characterized by reduced expression of CD80, CD86, and H-2Db (MHC class I), increased expression of CCR9, as well as producing IL-10 and having migratory activity to thymus cells. Transfected DCs induced T-regulatory cells (T-reg) and increased the intracellular content of IL-10 and TGF-b in CD4+T cells in their co-culture, and also suppressed their proliferative activity in response to antigen. The administration of tolDCs transfected with DNA constructs encoding type II collagen, IL-10, and CCR9 to mice with ACIA demonstrated a reduction in paw swelling, a reduction in the level of antibodies to type II collagen, and a regression of histological changes. Conclusion: The study presents an approach by which DCs transfected with DNA constructs encoding epitopes of type II collagen, IL-10 and CCR9 promote the development of antigen-specific tolerance, control inflammation and reduce the severity of experimental arthritis through the studied mechanisms: induction of T-reg, IL-10, TGF-b. [ABSTRACT FROM AUTHOR]

Byline: Amir Z. Maksyutov, Alexander G. Bachinsky, Alexander A. Chepurnov Ebola Virus (EBOV) presents a challenge for vaccine development because immune correlates of protection in humans are not well known. In earlier studies we developed a concept of local similarity which refers to resemblance of structural patterns of unrelated proteins as a function of their amino acid composition. The search for local similarities between human and EBOV proteins was performed. The resemblance of NP protein of EBOV to vascular endothelial growth factor and its receptor, which play a key role in the regulation of vascular permeability, was identified. A high degree of local similarity of Ebola GP protein with the tactile protein of the T-cell surface was also revealed. The similarity of the Ebola VP24 protein fragment with complement receptor type 1 (CD35 antigen) appears to be correlated with early activation of complement in lethal Ebola fever. This finding supports our prior studies indicating that VP24 determines the difference between lethal and non-lethal strains of EBOV. Several other similarities of potential significance were identified that might play an important role in the aetiology of Ebola-induced disease. In conclusion, local similarities between EBOV and human host proteins may provide a key to rational design of safe and effective filovirus vaccines. Such a vaccine must be free from epitopes that could potentially trigger Ebola-like hemorrhagic fever due to an autoimmune reaction induced by vaccination and other unanticipated adversities.