The role of active herpesvirus infection in the formation of atopic dermatitis and psoriasis

The results of previous studies suggest the involvement of herpes viruses in the development of atopic dermatitis and psoriasis, but there is no convincing evidence. Aim of the study was to evaluate the role of active herpesvirus infection in exacerbation of atopic dermatitis and psoriasis. Material and methods. The analysis of the incidence of infectious mononucleosis, genital herpes, cytomegalovirus infection, skin and subcutaneous tissue diseases, atopic dermatitis, psoriasis in Russia in 2000–2020 was carried out. 92 blood donors and 97 patients with skin and subcutaneous tissue diseases (44 with atopic dermatitis and 53 with psoriasis) were examined for the presence of immunoglobulins M and G to herpes simplex viruses (HSV1,2), Epstein-Barr (EBV), cytomegalovirus (CMV), human herpes type 6 (HНV6). Results and discussion. A significant strong direct correlation was revealed between the incidence of genital herpes and diseases of the skin and subcutaneous tissue (p = 0.85), atopic dermatitis (p = 0.85); infectious mononucleosis and psoriasis (p = 0.85). The frequency of detection of IgM to HSV1,2, in total, IgG EA and IgM VCA EBV in the group of patients is significantly higher than in donors (p < 0.05). In patients with atopic dermatitis, IgM to HSV1 were detected significantly more often than in individuals with psoriasis, and markers of active EBV infection were significantly less common. The presence of IgM HSV-1 statistically significantly increases the incidence of atopic dermatitis (relative risk (RR) = 2.3, 95 % confidence interval (95 % CI) 1.6–3.3)), IgM VCA and IgG EA EBV – the incidence of psoriasis (RR = 2.3, 95 % CI 1.5–3.3). Conclusions. It has been shown for the first time that active HSV1,2 infection is a trigger factor for the development of atopic dermatitis, EBV infection is psoriasis

Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity

Background Immunotherapy represents the future of clinical cancer treatment. The type of cancer cell death determines the antitumor immune response and thereby contributes to the efficacy of anticancer therapy and long-term survival of patients. Induction of immunogenic apoptosis or necroptosis in cancer cells does activate antitumor immunity, but resistance to these cell death modalities is common. Therefore, it is of great importance to find other ways to kill tumor cells. Recently, ferroptosis has been identified as a novel, iron-dependent form of regulated cell death but whether ferroptotic cancer cells are immunogenic is unknown. Methods Ferroptotic cell death in murine fibrosarcoma MCA205 or glioma GL261 cells was induced by RAS-selective lethal 3 and ferroptosis was analyzed by flow cytometry, atomic force and confocal microscopy. ATP and high-mobility group box 1 (HMGB1) release were detected by luminescence and ELISA assays, respectively. Immunogenicity in vitro was analyzed by coculturing of ferroptotic cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and activation/maturation of BMDCs (CD11c + CD86 +, CD11c + CD40 +, CD11c + MHCII +, IL-6, RNAseq analysis). The tumor prophylactic vaccination model in immune-competent and immune compromised (Rag-2 -/-) mice was used to analyze ferroptosis immunogenicity. Results Ferroptosis can be induced in cancer cells by inhibition of glutathione peroxidase 4, as evidenced by confocal and atomic force microscopy and inhibitors' analysis. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2 -/- mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells. Conclusions These results pave the way for the development of new therapeutic strategies for cancers based on induction of ferroptosis, and thus broadens the current concept of immunogenic cell death and opens the door for the development of new strategies in cancer immunotherapy

In Vitro Models of Brain Disorders

The brain is the most complex organ of the body, and many pathological processes underlying various brain disorders are poorly understood. Limited accessibility hinders observation of such processes in the in vivo brain, and experimental freedom is often insufficient to enable informative manipulations. In vitro preparations (brain slices or cultures of dissociated neurons) offer much better accessibility and reduced complexity and have yielded valuable new insights into various brain disorders. Both types of preparations have their advantages and limitations with regard to lifespan, preservation of in vivo brain structure, composition of cell types, and the link to behavioral outcome is often unclear in in vitro models. While these limitations hamper general usage of in vitro preparations to study, e.g., brain development, in vitro preparations are very useful to study neuronal and synaptic functioning under pathologic conditions. This chapter addresses several brain disorders, focusing on neuronal and synaptic functioning, as well as network aspects. Recent progress in the fields of brain circulation disorders, excitability disorders, and memory disorders will be discussed, as well as limitations of current in vitro models