Immune-mediated Damage Research Articles

JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia

AbstractThe hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signaling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients revealed an active JAK-STAT1 signaling signature along with upregulation of antigen presentation and downregulation of key components of the EGFR pathway. Our findings offer molecular insights and highlight a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.

Local Controlled Delivery of IL-4 Decreases Inflammatory Bone Loss in a Murine Model of Periodontal Disease.

Chronic inflammatory diseases are a leading global health problem. In many of these diseases, the consistent presence of systemic low-grade inflammation induces tissue damage. This is true in conditions such as diabetes, arthritis, and autoimmune disorders, where an overactive and uncontrolled host immune response is a major driver of immunopathology. Central to this overactive and destructive host response are macrophages, the major phagocytic cells within the innate immune system. These cells exhibit a dual role in both host defense against invading pathogens and promotion of tissue repair during inflammation resolution. Those unique characteristics make macrophages an excellent target for therapeutic interventions in many chronic inflammatory conditions. Using periodontal disease as a model of chronic inflammation, we sought to assess the feasibility of using a controlled drug delivery strategy to target macrophages within the oral cavity. To that end, IL-4 was encapsulated within a biodegradable polymer carrier and locally delivered into the inflamed periodontal tissues. Our data indicate that local sustained delivery of IL-4 decreased inflammatory bone loss and promoted bone gain in the diseased mouse periodontium. Those effects correlated with a shift of local macrophage population toward a prorepair phenotype. Using single-cell RNA sequencing technology, we found that IL-4 delivery reversed several proinflammatory pathways associated with tissue destructive macrophages. Together, our data suggest that sustained delivery of IL-4 may be a viable therapeutic option for chronic diseases characterized by immune-mediated tissue damage.

Immunometabolism and mitochondria in inflammatory bowel disease: a role for therapeutic intervention?

Inflammatory bowel diseases (IBDs), incurable conditions characterised by recurrent episodes of immune-mediated gut inflammation and damage of unknown aetiology, are common. Current advanced therapies target key leukocyte-trafficking and cytokine-signalling hubs but are only effective in 50% of patients. With growing evidence of mitochondrial dysfunction in IBD and advances in our understanding of the role of metabolism in inflammation, we provide an overview of novel metabolic approaches to IBD therapy, challenging the current 'therapeutic ceiling', identifying critical pathways for intervention and re-imagining metabolic biomarkers for the 21st century.

Emapalumab as a therapeutic intervention for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A case series.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is characterized by a severe cytokine storm, heightened inflammatory response, and immune-mediated damage to tissues and organs. Standard treatment protocols for hemophagocytic lymphohistiocytosis often fall short in effectively controlling EBV-HLH, leading to a need for novel therapeutic options. Emapalumab, a monoclonal antibody targeting interferon-gamma, has shown promise due to its targeted cytokine modulation capabilities and favorable safety profile. This study aimed to evaluate the efficacy and safety of emapalumab in pediatric patients with EBV-HLH. The case series involved 4 pediatric patients diagnosed with EBV-HLH who did not achieve disease control despite receiving comprehensive treatment. All 4 pediatric patients were diagnosed with EBV-HLH. Emapalumab was introduced as an adjunctive therapeutic intervention alongside the HLH-94 or L-DEP regimens for these patients. Among the 4 patients, 1 experienced severe multiorgan dysfunction and opted to discontinue therapy. The remaining 3 patients showed controlled disease progression with significant clinical improvements following emapalumab administration. These improvements included reduced levels of inflammatory markers, normalization of blood counts and liver function, and decreased Epstein-Barr virus viral load. The findings suggest that emapalumab may be an effective and safe treatment option for pediatric EBV-HLH. However, further research is necessary to confirm these outcomes, especially in critically ill patients.

Predictors and Management of Inadequate Response to JAK Inhibitors in Alopecia Areata.

Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care.

Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of β cell damage during viral exposure.

Microglia LILRB4 upregulation reduces brain damage after acute ischemic stroke by limiting CD8+ T cell recruitment

BackgroundLeukocyte immunoglobulin-like receptor B4 (LILRB4) plays a significant role in regulating immune responses. LILRB4 in microglia might influence the infiltration of peripheral T cells. However, whether and how LILRB4 expression aggravates brain damage after acute ischemic stroke remains unclear. This study investigates the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice.Methods and resultsMicroglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed by a Cre-loxP system. Then, they were used to investigate the role of LILRB4 after ischemic stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. Single-cell RNA sequencing (scRNA-seq) identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. Flow cytometry and immunofluorescence staining showed increased CD8+ T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. T cell migration assays demonstrated that LILRB4-KD microglia promoted CD8+ T cell recruitment and activation in vitro, which was mitigated by CCL2 inhibition and recombinant arginase-1 addition. The scRNA-seq and spatial transcriptomics identified CCL2 was predominantly secreted from activated microglia/macrophage and increased CCL2 expression in LILRB4-KD microglia, suggesting a chemokine-mediated mechanism of LILRB4.ConclusionLILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8+ T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8+ T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke.

Therapeutic delivery of CCL2 modulates immune response and restores host-microbe homeostasis.

Many chronic inflammatory diseases are attributed to disturbances in host-microbe interactions, which drive immune-mediated tissue damage. Depending on the anatomic setting, a chronic inflammatory disease can exert unique local and systemic influences, which provide an exceptional opportunity for understanding disease mechanism and testing therapeutic interventions. The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host-microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger nonresolving chronic inflammation, progressive bone loss, and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine (C-C motif) ligand 2 (CCL2) in murine ligature-induced PD using clinically relevant models as a preventive, interventional, or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment up-regulated M2-macrophage and downregulated proinflammatory and pro-osteoclastic markers. Furthermore, single-cell ribonucleic acid (RNA) sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting the triggering receptor expressed on myeloid cells-1 (TREM-1) signaling in classically activated macrophages and inducing protein kinase A (PKA) signaling in infiltrating macrophages. Finally, 16S ribosomal ribonucleic acid (rRNA) sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2-treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis.

Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets exposed to SARS-CoV-2 or Coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared to separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune cell-mediated host damage and uncovered mechanism of β cell damage during viral exposure.

Astrocyte-derived factors regulate CNS myelination.

The role that astrocytes play in central nervous system (CNS) myelination is poorly understood. We investigated the contribution of astrocyte-derived factors to myelination and revealed a substantial overlap in the secretomes of human and rat astrocytes. Using in vitro myelinating co-cultures of primary retinal ganglion cells and cortical oligodendrocyte precursor cells, we discovered that factors secreted by resting astrocytes, but not reactive astrocytes, facilitated myelination. Soluble brevican emerged as a new enhancer of developmental myelination in vivo, CNS and its absence was linked to remyelination deficits following an immune-mediated damage in an EAE mouse model. The observed reduction of brevican expression in reactive astrocytes and human MS lesions suggested a potential link to the compromised remyelination characteristic of neurodegenerative diseases. Our findings suggested brevican's role in myelination may be mediated through interactions with binding partners such as contactin-1 and tenascin-R. Proteomic analysis of resting versus reactive astrocytes highlighted a shift in protein expression profiles, pinpointing candidates that either facilitate or impede CNS repair, suggesting that depending on their reactivity state, astrocytes play a dual role during myelination.

Immune checkpoint inhibitor therapy‑related pneumonitis: How, when and why to diagnose and manage (Review).

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by enhancing the immune response against tumor cells. However, their influence on immune pathways can lead to immune-related adverse events such as pneumonitis, necessitating rapid diagnosis and management to prevent severe complications. These adverse events arise from the activation of the immune system by immunotherapeutic drugs, leading to immune-mediated inflammation and tissue damage in various organs and tissues throughout the body. The present review article discusses the pathophysiology, clinical presentation, diagnostic modalities and management strategies for ICI-related pneumonitis, emphasizing early recognition and tailored interventions. Future research endeavors should focus on elucidating the underlying mechanisms of pneumonitis and identifying predictive biomarkers to guide personalized treatment strategies in this evolving field of oncology.

Chinese herbal formula, modified Guilu Erxian glue, alleviates apoptosis of hematopoietic stem cells by regulating SLAM-SAP signal pathway in aplastic anemia mice model

Ethnopharmacological relevanceGuilu Erxian Glue (GEG) and Danggui Buxue Tang (DBT) are traditional Chinese herbal formulas. According to the theory of traditional Chinese medicine, the combination of those two formulas (Modified Guilu Erxian Glue, MGEG) has the effects of tonifying the kidney and producing blood, was usually used to treat bone marrow failure diseases, including aplastic anemia (AA). Aim of the studyT lymphocytes play a crucial role in the disease pathogenesis and progression of AA. Our preliminary results confirmed that GEG can improve the damage of hematopoietic stem cells in mice, while DBT can reduce the proliferation and differentiation of T lymphocytes and inhibit the production of IFN-γ. We hypothesized that the combination of those two herbal formulas could inhibit immune attack and restore hematopoietic function through multiple mechanisms. In this study, we aim to study the curative effect of MGEG on regulating the expression of Signal lymphocyte activating molecule (SLAM), an activation-related molecule in T lymphocytes, thereby suppressing the immune function of T cells and decelerating the damage to hematopoietic stem cells. Materials and methodsHigh-performance liquid chromatography-electrospray ionization/mass spectrometry system was used to identify the components of the MGEG formulation. Induction of aplastic anemia mouse model by injecting allogeneic lymphocyte suspension into BABL/c mice after ionizing radiation. Cyclosporine A (CsA) was used as a positive control drug. Flow cytometry was used to detect the number and apoptosis rate of hematopoietic stem cells in the bone marrow. Enzyme-linked immunosorbent assay was performed to measure the levels of IFN-γ and TNF-α. Immunofluorescence staining was used to assess the expression of T-bet and SLAM-SAP. Western Blot was conducted to examine the expression of activation-related molecules in T lymphocytes and proteins related to the Fas signal pathway. Hematoxylin-eosin staining was performed to observe pathological changes in the bone marrow tissue. Wright-Giemsa staining was utilized to evaluate alterations in the cellular composition and basic structure of the bone marrow cells (BMCs). Transmission electron microscopy was employed to observe changes in the structure and morphology of hematopoietic stem cells. The hematology analyzer was used to detect peripheral blood parameters. ResultsTwenty-three different components were identified in MGEG. After MGEG treatment, the expression levels of Fyn and SLAM-SAP binding were increased in AA mice, while the expression levels of T-bet were decreased and the secretion of IFN-γ was reduced significantly. Additionally, MGEG also could downregulate the protein levels of Fas, caspase-3, and cleaved caspase-3 in AA mice. ConclusionMGEG could attenuate the production of IFN-γ by promoting the SLAM-SAP signal pathway to regulate the generation and distribution of T-bet in T cells. Additionally, it suppresses apoptosis of HSCs through intervention in the Fas-dependent pathway, thereby mitigating immune-mediated damage to HSCs.

A Role of Physical Activity in Patients with Systemic Lupus Erythematosus – A Literature Review

Introduction: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease of unknown cause. Inflammation and immune-mediated damage to multiple organ systems are the hallmarks of this condition. It is capable of affecting virtually every organ of the body, including but not limited to the hematologic, kidney, mucocutaneous, musculoskeletal, and kidney systems. Immunologic abnormalities, specifically the production of numerous antinuclear antibodies Purpose of work: Collect information on the impact of physical exercise and diet on SLE patients and the possibilities of their therapeutic use. Summary: Being active helps patients with SLE maintain a lower body weight, improve their mental state, relieve their fatigue, and increase their general satisfaction. There are some findings that indicate that physical activity is not as important in therapy for patients with SLE as adding exercise to the basic treatment program. Nevertheless, physical activity is beneficial for the overall well-being of individuals, regardless of whether they have SLE or not. Therefore, it is recommended that patients with SLE engage in physical activity, as it has been widely acknowledged to have significant positive health benefits.

Unveiling the role of mtDNA in Liver-Kidney Crosstalk: Insights from trichloroethylene hypersensitivity syndrome

In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance. This study seeks to elucidate the role of mtDNA in conditions marked by liver-kidney crosstalk. In previous clinical cases, it has been observed that patients with Trichloroethylene Hypersensitivity Syndrome (TCE-HS) who experience severe liver injury often also exhibit renal injury. In this study, patients diagnosed with trichloroethylene hypersensitivity syndrome were recruited from Shenzhen Occupational Disease Control Center. And Balb/c mice were treated with trichloroethylene. The correlation between liver and kidney injuries in patients with TCE-HS was assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Alterations in mtDNA levels were examined in mouse hepatocytes, red blood cells (RBCs), and renal tubular epithelial cells utilizing immunofluorescence and PCR techniques. TCE-sensitized mice exhibited a significant increase in reactive oxygen species (ROS) and the opening of the mitochondrial permeability transition pore in hepatocytes, resulting in the release of mtDNA. Furthermore, heightened levels of mtDNA and Toll-like Receptor 9 (TLR9) expression were observed in RBCs. Additional experiments demonstrated elevated expression of TLR9 and its downstream mediator MyD88 in renal tubule epithelial cells of TCE-sensitized mice. In vitro investigations confirmed that mtDNA activates the TLR9 pathway in TCMK-1 cells. Collectively, these results suggest that mtDNA released from mitochondrial damage in hepatocytes is carried by RBCs to renal tubular epithelial cells and mediates inflammatory injury in renal tubular epithelial cells through activation of the TLR9 receptor.

RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease

Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Case Report: Asymptomatic SARS-COV2 infection triggering recurrent Takotsubo syndrome

Takotsubo syndrome (TTS) is a rare disease mimicking acute coronary syndrome, often triggered by physical or emotional stress, and characterized by transient left ventricular dysfunction. Recurrences are described in about 5% of cases and may have different clinical and imaging patterns. In the present report, SARS-COV-2 infection, even in the absence of symptoms and overt emotional stress, seems correlated with recurrence of TTS, due to the absence of other recognized triggers. The hypothesis is that in predisposed patients, events like catecholamine-induced myocyte injury, direct viral damage, cytokine storm, immune-mediated damage, and procoagulant state, all possibly induced by the infection, may elicit endothelial dysfunction as substrate for TTS onset.

Interplay between the Chaperone System and Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus Pathogenesis: Is Molecular Mimicry the Missing Link between Those Two Factors?

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by self-immune tolerance breakdown and the production of autoantibodies, causing the deposition of immune complexes and triggering inflammation and immune-mediated damage. SLE pathogenesis involves genetic predisposition and a combination of environmental factors. Clinical manifestations are variable, making an early diagnosis challenging. Heat shock proteins (Hsps), belonging to the chaperone system, interact with the immune system, acting as pro-inflammatory factors, autoantigens, as well as immune tolerance promoters. Increased levels of some Hsps and the production of autoantibodies against them are correlated with SLE onset and progression. The production of these autoantibodies has been attributed to molecular mimicry, occurring upon viral and bacterial infections, since they are evolutionary highly conserved. Gut microbiota dysbiosis has been associated with the occurrence and severity of SLE. Numerous findings suggest that proteins and metabolites of commensal bacteria can mimic autoantigens, inducing autoimmunity, because of molecular mimicry. Here, we propose that shared epitopes between human Hsps and those of gut commensal bacteria cause the production of anti-Hsp autoantibodies that cross-react with human molecules, contributing to SLE pathogenesis. Thus, the involvement of the chaperone system, gut microbiota dysbiosis, and molecular mimicry in SLE ought to be coordinately studied.

Impact of nutritional risk factors on the development of multiple sclerosis

The literature review considers the data on the assessment of the influence of alimentary factors on the development of a severe neurological disease - multiple sclerosis (MS). MS is a polyetiologic disease, the risk of development of which is influenced by both infectious (Epstein-Barr virus, herpes simplex virus, influenza virus, etc.) and noninfectious factors (genetic predisposition, smoking, geographic region of residence, etc.). MS is a progressive demyelinating disease of the central nervous system (CNS), which leads to neurodegeneration accompanied by a variety of clinical manifestations. The pathogenesis of MS is characterized by immune-mediated damage to the myelin sheaths of nerve fibers, which is manifested by inflammation, neurosynaptic damage, and destruction of white matter, axons, and blood vessels. Rapid non-evolutionary dietary and lifestyle changes, which are driven by urbanization, industrialization and globalization of the food market, are leading to an increase in most chronic non-communicable diseases, including MS. The effects induced by alimentary factors are due to changes in the microbial composition of the gastrointestinal tract (GIT), immune cell function, enzyme systems functioning, etc. The aim of the work is to study the influence of micro/macronutrients, as well as the nature of the diet on the risk of MS development, to assess the role of nutrition in the primary prevention of MS. It has been shown that a diet characterized by a high content of animal fats and trans-isomers of fatty acids (TFA), increased consumption of meat products, but low content of vegetables, fruits and whole-grain products is associated with a higher risk of MS development. Regular inclusion in the diet of sources of polyunsaturated fatty acids (PUFAs) (vegetable oils, seeds, nuts, marine fish) and vitamin D (fatty fish, caviar, butter, egg yolk) leads to lower relapse rates and less new brain lesions among MS patients. The literature review was conducted using open sources posted in electronic databases: PubMed, Medline, Scopus, Google Scholar, World Bank publications, WHO, eLibrary, Cyberleninka, Web of Science.

Association between rheumatic musculoskeletal diseases and air pollution: myth or reality?

This review discusses the impact of air pollution exposure on rheumatic musculoskeletal diseases, and also considers air pollution assessment and its limitations. Rheumatic diseases are caused by dysregulation and excessive activation of the immune system, leading to systemic inflammation and immune-mediated damage. Air pollution, particularly particulate matter originating from fossil fuel combustion, increases the production of inflammatory cytokines and activates pathways involved in the inflammatory response. Long-term and short-term exposure to air pollution can be evaluated using various methodologies. Despite the limitations of exposure assessment, the review highlights the importance of monitoring air pollution levels to mitigate their harmful effects on human health and the environment. KEY WORDS: Autoimmune diseases, rheumatic musculoskeletal diseases (RMDs), pollution, environment.