Immuno, Volume 5, Issue 1 (March 2025) – 6 articles

Systemic autoimmune diseases (SAIDs) affect millions worldwide, presenting significant clinical challenges due to their complex pathogenesis and limited treatment options. Traditional immunosuppressive therapies, while effective, often lack precision, leading to significant side effects and inadequate disease control. Recent advances in synthetic immunology offer promising avenues for precise, targeted interventions in SAIDs. This review examines the latest innovations in synthetic immunology for treating autoimmune diseases, focusing on engineered immune cells, synthetic biologics, and gene-editing technologies. It explores the therapeutic potential of these approaches to modulate immune tolerance, reduce systemic inflammation, and enhance patient-specific treatment efficacy. However, despite these promising developments, challenges remain, including immune system complexity, safety concerns, and regulatory hurdles that may hinder clinical translation. This review aims to consolidate current advancements, address existing barriers, and outline potential future directions for synthetic immunology in autoimmune disease management, highlighting synthetic immunology’s role in transforming the therapeutic landscape for SAIDs. Full article

Social behavior restrictions, social distancing, and promotion of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic have significantly reduced the incidence of many epidemic infections in the world, especially in children. Resurges of infectious diseases vary depending on the biological characteristics of each infectious pathogen and differences in culture, lifestyle, and infection control mitigation policies by country or region. Although the gapping of infectious disease outbreaks can cause children who were uninfected during that period to become more susceptible to infection after the pandemic, resulting in a slightly older age of infected children, there are no conclusive reports that suggest a definite impact on the development of children’s immune maturation or its balance. Insufficient immune challenges in early life may influence the risk of developing immune-mediated conditions such as allergies or autoimmune diseases later in life, though evidence for this is still emerging. Future observational studies are needed to determine the long-term impact of the epidemic gap caused by the COVID-19 pandemic as well as the long-term impact of COVID-19 infection itself on the immune function or balance of children. Full article

Sex-based differences in innate immunity may play a crucial role in susceptibility to and progression of tuberculosis (TB), a disease that disproportionately affects men. This study aimed to examine whether early host–pathogen interactions contribute to the heightened vulnerability of males to Mycobacterium tuberculosis (Mtb) infection. Using recombination activating gene 2 knockout (RAG2 KO) mice, which lack adaptive immunity, we were able to isolate and analyze innate immune responses to Mtb without the influence of T and B cells. Surprisingly, and in stark contrast to wild-type mice that reflect the male bias as observed in humans, female RAG2 KO mice were more susceptible to Mtb than their male counterparts. Increased lung CFU in females was accompanied by a significant rise in inflammation, indicated by elevated levels of inflammatory cytokines and chemokines, as well as a massive influx of neutrophils into the lungs. In contrast, male mice exhibited higher levels of IFN-γ and CCL5, along with a greater presence of NK cells in their lungs, suggesting that, in the absence of adaptive immunity, males benefit from a more robust NK cell response, potentially offering greater protection by better controlling inflammation and slowing disease progression. Full article

Lawsonia intracellularis is a Gram-negative, intracellular bacterium that can infect several animal species. In pigs, the bacteria cause porcine proliferative enteropathy, or ileitis. The wide spread of the pathogen produces a large impact on pig production worldwide. Saliva is a source of biomarkers that can help to monitor changes in the immune system after vaccination. The purpose of this study was to study the changes in haptoglobin (Hp), immunoglobulin G (IgG), and adenosine deaminase (ADA) in saliva after vaccination against Lawsonia intracellularis. In addition, productivity parameters were analysed to evaluate if vaccination and changes in salivary analytes could be associated with changes in these parameters. The pigs vaccinated against Lawsonia showed an improvement in the productive parameters and a reduction in food conversion and frequency of diseases. In addition, they showed lower values of Hp (p = 0.011), IgG (p < 0.01), and ADA (p < 0.003) in saliva during the first two months of the fattening period compared to non-vaccinated pigs. It could be concluded that in our experimental conditions, the vaccination against Lawsonia intracellularis produced a significant decrease in biomarkers of the immune response in saliva compared with the non-vaccinated pigs. This would indicate a reduction in the activation of the immune system, which could be postulated to be due to the increased defence ability of the organism against pathogens. This reduced activation of the immune system can lead to better food conversion and an increase in the productive parameters of these pigs. Overall, this report opens a new window for the possible use of saliva for non-invasive evaluation of the immune system after vaccination in pigs. Full article

Dendritic cells (DCs) play a crucial role in controlling viral infections. Little is known about the changes in frequencies of the DC subsets in patients with chronic hepatitis C (CHC), particularly in the era of interferon-free regimens. We aimed to evaluate the impact of sofosbuvir/daclatasvir on the frequency of different peripheral DC subsets, the expression of the inhibitory CD200R and its ligand CD200 on DC, and their relation to the treatment outcome. A total of 1000 patients with CHC were enrolled and treated with a fixed oral dose of 400 mg of sofosbuvir and 60 mg of daclatasvir for 12 weeks. A total of 940 patients achieved sustained virologic response (SVR), and only 60 patients were non-responders (NRs). The frequencies of the peripheral plasmacytoid (pDC) and myeloid (mDCs) subsets and their surface expressions of CD200R and CD200 molecules were analyzed using flow cytometry. This analysis included 60 non-responders (NR group), 60 randomly selected sustained virologic responders (SVR group) at baseline, and at the end of treatment, and 60 healthy controls. HCV infection was associated with a down-regulation in the frequency of mDC, compared to healthy controls. In addition, mDC in HCV-infected patients showed lower levels of CD200R. However, neither the pDC frequency nor their CD200R expression was significantly altered. Interestingly, by the end of therapy, the frequencies of circulating mDCs and CD200R⁺mDC increased significantly in the SVR group and were even comparable to healthy controls. The levels of these cells were not normalized in the NR group. Percentages of mDCs and CD200R⁺mDC subsets showed good prognostic accuracy for predicting virologic response to therapy. Our results showed that HCV infection was associated with modulation of the mDC frequency and their surface expression of CD200R. Successful daclatasvir and sofosbuvir combined therapy was associated with the normalization of the percentages of mDC and CD200R⁺mDC. Full article

Exostosin 1 (EXT1) encodes a type II transmembrane glycosyltransferase residing in the endoplasmic reticulum and plays an essential role in the elongation of heparan sulfate chain biosynthesis. Additionally, EXT1 may act as an oncogene that could promote cell proliferation as well as cancer cell metastasis. Herein, we investigated EXT1’s expression pattern and prognostic value in breast cancer, along with its immunological implications. Immunohistochemical staining of EXT1 was assessed in 85 breast cancer patients. Patients were categorized into molecular subtypes, namely luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2), along with triple-negative breast cancer (TNBC). Correlations of EXT1 immunostaining with clinicopathological parameters were evaluated. Furthermore, the correlations of EXT1 expression with tumor immune infiltration and immune cell surface markers were assessed using TIMER. Moreover, survival analysis was conducted to reveal EXT1’s prognostic value. EXT1 expression was markedly associated with the status of the estrogen receptor (ER), molecular subtypes, and recurrence status. In addition, high levels of EXT1 expression were associated with worse overall survival (OS) and relapse-free survival (RFS). Analysis of immune infiltration indicated that EXT1 expression was positively correlated with dendritic cells (DCs), macrophages, neutrophils, CD4⁺ T cells, and CD8⁺ T cells, although it showed a negative correlation with the tumor purity. Overall, this study suggests that the elevated EXT1 expression, particularly in TNBC, has a positive correlation with poor prognosis and with immune-infiltrated cells in breast cancer. Therefore, it may emerge as an independent prognostic biomarker, immunological marker, and potential future therapeutic target for the most aggressive TNBC subtype. Full article