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Cells Jul 2023T cells are critical players in adaptive immunity, driving the tissue injury and organ damage of patients with autoimmune diseases. Consequently, investigations on T... (Review)
Review
T cells are critical players in adaptive immunity, driving the tissue injury and organ damage of patients with autoimmune diseases. Consequently, investigations on T cell activation, differentiation, and function are valuable in uncovering the disease pathogenesis, thus exploring promising therapeutics for autoimmune diseases. In recent decades, accumulating studies have pinpointed immunometabolism as the fundamental determinant in controlling T cell fate. Specifically, mitochondria, as a hub of intracellular metabolism, connect glucose, lipid, and amino acid metabolic pathways. Herein, we summarize metabolic adaptations of mitochondrial oxidative phosphorylation and the relevant glucose, lipid, and amino acid metabolism during T cell activation, differentiation, and function. Further, we focused on current updates of the molecular bases for metabolic reprogramming in autoimmune T cells and advances in exploring metabolic-targeted therapeutics against autoimmune diseases. This might facilitate the in-depth understanding of autoimmune pathogeneses and the clinical management of autoimmune diseases.
Topics: Humans; T-Lymphocytes; Mitochondria; Autoimmune Diseases; Amino Acids; Lipids
PubMed: 37443834
DOI: 10.3390/cells12131800 -
Advanced Drug Delivery Reviews Jun 2024Neutrophils play an essential role as 'first responders' in the immune response, necessitating many immune-modulating capabilities. Chronic, unresolved inflammation is... (Review)
Review
Neutrophils play an essential role as 'first responders' in the immune response, necessitating many immune-modulating capabilities. Chronic, unresolved inflammation is heavily implicated in the progression and tissue-degrading effects of autoimmune disease. Neutrophils modulate disease pathogenesis by interacting with the inflammatory and autoreactive cells through effector functions, including signaling, degranulation, and neutrophil extracellular traps (NETs) release. Since the current gold standard systemic glucocorticoid administration has many drawbacks and side effects, targeting neutrophils in autoimmunity provides a new approach to developing therapeutics. Nanoparticles enable targeting of specific cell types and controlled release of a loaded drug cargo. Thus, leveraging nanoparticle properties and interactions with neutrophils provides an exciting new direction toward novel therapies for autoimmune diseases. Additionally, recent work has utilized neutrophil properties to design novel targeted particles for delivery into previously inaccessible areas. Here, we outline nanoparticle-based strategies to modulate neutrophil activity in autoimmunity, including various nanoparticle formulations and neutrophil-derived targeting.
Topics: Humans; Nanoparticles; Neutrophils; Autoimmune Diseases; Animals; Autoimmunity; Drug Delivery Systems
PubMed: 38663550
DOI: 10.1016/j.addr.2024.115316 -
The Journal of Dermatological Treatment Dec 2024Dermatomyositis, systemic and cutaneous lupus erythematosus have a significantly higher prevalence in women than men, emphasizing the relevance of exploring the... (Review)
Review
INTRODUCTION
Dermatomyositis, systemic and cutaneous lupus erythematosus have a significantly higher prevalence in women than men, emphasizing the relevance of exploring the relationship between sex hormones and autoimmune skin diseases. This review analyzes the interplay between sex hormones and these two skin diseases.
MATERIALS AND METHODS
We performed an extensive literature search using the PubMed database from July to August 2023. Search terms included 'contraceptives', 'pregnancy', 'hormone replacement', 'tamoxifen', and 'aromatase inhibitors'.
RESULTS AND DISCUSSION
This comprehensive literature review shows that there remains considerable debate regarding the use of hormonal contraceptives and hormonal replacement therapy in individuals with autoimmune skin conditions. Nonetheless, it is well established that their use is contraindicated in patients with antiphospholipid syndrome or when antiphospholipid antibodies are positive. Individuals experiencing disease flares and uncontrolled symptoms should also avoid these interventions. Pregnancy planning should be timed to coincide with well-managed disease states to minimize obstetric and neonatal complications. Hormonal breast cancer treatment requires close skin monitoring.
CONCLUSION
Pregnancy, menopause, contraceptive use, hormone replacement therapy, and breast cancer treatment drugs result in substantial shifts in hormone levels. Additionally, hormone levels are altered by aromatase inhibitors and anti-estrogen medications. These fluctuations can modulate mechanisms influencing autoimmune skin abnormalities.
Topics: Pregnancy; Male; Infant, Newborn; Humans; Female; Hormones; Autoimmune Diseases; Gonadal Steroid Hormones; Menopause; Breast Neoplasms; Lupus Erythematosus, Systemic
PubMed: 38317519
DOI: 10.1080/09546634.2024.2312241 -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is an autoimmune disease that can induce joint deformities and functional impairment, significantly impacting the overall well-being of... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease that can induce joint deformities and functional impairment, significantly impacting the overall well-being of individuals. Exosomes, which are cellularly secreted vesicles, possess favorable biological traits such as biocompatibility, stability, and minimal toxicity. Additionally, they contain nucleic acids, lipids, proteins, amino acids, and metabolites, serving as mediators in cellular communication and information exchange. Recent studies have demonstrated the association between exosomes and the pathogenesis of RA. Exosomes derived from mesenchymal stem cells, dendritic cells, and neutrophils exert influence on the biological functions of immune cells and joint cells, however, the precise mechanism remains largely unclarified. This comprehensive review systematically analyzes and summarizes the biological characteristics and functionalities of exosomes derived from diverse cellular sources, thus establishing a scientific foundation for the utilization of exosomes as diagnostic targets and therapeutic modalities in the context of RA.
Topics: Humans; Exosomes; Arthritis, Rheumatoid; Autoimmune Diseases; Cell Communication
PubMed: 37575235
DOI: 10.3389/fimmu.2023.1240747 -
Frontiers in Immunology 2023Epidemiological studies suggested a potential connection between education and autoimmune disorders. This study investigated the possible cause-and-effect relationship...
OBJECTIVES
Epidemiological studies suggested a potential connection between education and autoimmune disorders. This study investigated the possible cause-and-effect relationship using a Mendelian randomization approach.
METHODS
We explored the causality between four education traits (n = 257,841~1,131,881) and 22 autoimmune diseases. The mediating role of smoking (632,802 individuals), BMI (681,275 individuals), alcohol (335,394 individuals), and income (397,751 individuals) was also investigated. Transcriptome-wide association study (TWAS) and enriched signaling pathways analysis were used to investigate the underlying biological mechanisms.
RESULTS
Especially, higher cognitive performance was protective for psoriasis (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.60-0.79, = 6.12×10), rheumatoid arthritis (RA) (OR = 0.75, 95% CI = 0.67-0.83, = 4.62×10), and hypothyroidism (OR = 0.83, 95% CI = 0.77-0.90, = 9.82×10). Higher levels of educational attainment decreased risks of psoriasis (OR = 0.61, 95% CI = 0.52-0.72, = 1.12×10), RA (OR = 0.68, 95% CI = 0.59-0.79, = 1.56×10), and hypothyroidism (OR = 0.80, 95% CI = 0.72-0.88, = 5.00×10). The completion of highest-level math class genetically downregulates the incidence of psoriasis (OR = 0.66, 95% CI = 0.58-0.76, = 2.47×10), RA (OR = 0.71, 95% CI = 0.63-0.81, = 5.28×10), and hypothyroidism (OR = 0.85, 95% CI = 0.79-0.92, = 8.88×10). Higher self-reported math ability showed protective effects on Crohn's disease (CD) (OR = 0.67, 95% CI = 0.55-0.81, = 4.96×10), RA (OR = 0.76, 95% CI = 0.67-0.87, = 5.21×10), and psoriasis (OR = 0.76, 95% CI = 0.65-0.88, = 4.08×10). Protein modification and localization, response to arsenic-containing substances may participate in the genetic association of cognitive performance on UC, RA, psoriasis, and hypothyroidism. According to mediation analyses, BMI, smoking, and income served as significant mediators in the causal connection between educational traits and autoimmune diseases.
CONCLUSION
Higher levels of education-related factors have a protective effect on the risk of several autoimmune disorders. Reducing smoking and BMI and promoting income equality can mitigate health risks associated with low education levels.
Topics: Humans; Genome-Wide Association Study; Educational Status; Autoimmune Diseases; Arthritis, Rheumatoid; Hypothyroidism; Psoriasis; Mendelian Randomization Analysis
PubMed: 38146362
DOI: 10.3389/fimmu.2023.1249017 -
The Journal of Rheumatology Sep 2023Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the... (Review)
Review
Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the presence of autoantibodies and clinical phenotypes such as more severe disease with increased disease activity and damage. We will review the role and potential drivers of IFN-I dysregulation in 5 prototypic autoimmune diseases: systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, primary Sjögren syndrome, and systemic sclerosis. We will also discuss current therapeutic strategies that directly or indirectly target the IFN-I system.
Topics: Humans; Autoimmunity; Interferon Type I; Autoimmune Diseases; Lupus Erythematosus, Systemic; Interferons; Antibodies; Phenotype
PubMed: 37399470
DOI: 10.3899/jrheum.2022-0827 -
Biomolecules Mar 2024Neutrophil extracellular traps (NETs) are intricate fibrous structures released by neutrophils in response to specific stimuli. These structures are composed of... (Review)
Review
Neutrophil extracellular traps (NETs) are intricate fibrous structures released by neutrophils in response to specific stimuli. These structures are composed of depolymerized chromatin adorned with histones, granule proteins, and cytosolic proteins. NETs are formed via two distinct pathways known as suicidal NETosis, which involves NADPH oxidase (NOX), and vital NETosis, which is independent of NOX. Certain proteins found within NETs exhibit strong cytotoxic effects against both pathogens and nearby host cells. While NETs play a defensive role against pathogens, they can also contribute to tissue damage and worsen inflammation. Despite extensive research on the pathophysiological role of NETs, less attention has been paid to their components, which form a unique structure containing various proteins that have significant implications in a wide range of diseases. This review aims to elucidate the components of NETs and provide an overview of their impact on host defense against invasive pathogens, autoimmune diseases, and cancer.
Topics: Extracellular Traps; Humans; Neutrophils; Animals; NADPH Oxidases; Neoplasms; Autoimmune Diseases; Inflammation
PubMed: 38672433
DOI: 10.3390/biom14040416 -
Frontiers in Immunology 2024
Topics: Humans; Autoimmune Diseases; Animals; Lung; Lung Diseases; Heart Diseases; Myocardium
PubMed: 38646522
DOI: 10.3389/fimmu.2024.1407748 -
Autoimmunity Reviews Oct 2023Laminin-332 is an important component of the basement membrane. Recently, autoantibodies to Laminin-332 have been described in several autoimmune diseases. Many of these... (Review)
Review
IMPORTANCE
Laminin-332 is an important component of the basement membrane. Recently, autoantibodies to Laminin-332 have been described in several autoimmune diseases. Many of these autoimmune diseases have a high incidence of malignancy. The importance of Laminin-332 autoantibodies and its relationship to malignancy is highlighted by using Laminin-332 Pemphigoid (LM-332Pg) as a prototype.
OBJECTIVE
To identify several autoimmune diseases that have autoantibodies to Laminin-332 present, and to determine the prevalence of malignancy in them. Using Laminin-332 Pemphigoid (LM-332Pg) as a prototype, to compare clinical profiles of LM-332Pg patients with and without cancer. By identifying the temporal detection of cancer, can the influence of autoantibodies to Laminin-332 on prognosis be determined.
EVIDENCE REVIEW
A literature search was conducted to identify autoimmune and inflammatory diseases in which autoantibodies to Laminin-332 were present. Subsequently, the rate of malignancy in these autoimmune diseases was determined. A search for publications on LM-332Pg patients to determine cancer rates and clinical outcomes to examine if a relationship can be proposed, was performed.
FINDINGS
Autoantibodies to Laminin-332 were detected in recent studies of systemic lupus erythematosus (SLE), psoriasis, bronchiolitis obliterans (BO), graft-vs-host disease (GVH), bullous pemphigoid (BP), lichen planus (LP), epidermolysis bullosa acquisita (EBA), and membranous glomerulonephropathy (MGN). A high incidence of cancer rate was reported in these autoimmune diseases including primary Sjögren's syndrome (pSS), systemic sclerosis (SS), dermatomyositis (DM), multiple sclerosis (MS), immune thrombocytopenia purpura (ITP), and rheumatoid arthritis (RA). Data analysis demonstrated that LM-332Pg patients had a higher risk of developing ovarian, uterine, lung, gastric cancers and leukemia. The incidence for breast cancer was lower, when compared with global cancer rates. Patients diagnosed with cancer after the presence of LM-332Pg had higher rates of mortality and lower rates of remission, compared to those diagnosed with cancer prior to the discovery/diagnosis of LM-332Pg. When studied, levels of Laminin-332 autoantibodies correlated with the presence or absence of malignancy.
CONCLUSIONS AND RELEVANCE
Preliminary analysis suggests that autoantibodies to Laminin-332 are present in multiple autoimmune diseases, which also have a high incidence of malignancy. Detailed analysis of available data highlights that patients who developed LM-332Pg after cancer was diagnosed, had a more favorable prognosis, compared to patients who developed cancer when LM-332Pg was previously present. Preliminary data would suggest that autoantibodies to Laminin-332 could serve as an important biomarker in certain patients, for correlation with possible incidence of malignancy.
Topics: Humans; Pemphigoid, Bullous; Laminin; Pemphigoid, Benign Mucous Membrane; Autoimmune Diseases; Autoantibodies; Paraneoplastic Syndromes; Neoplasms; Mucous Membrane
PubMed: 37673192
DOI: 10.1016/j.autrev.2023.103444 -
Investigative Ophthalmology & Visual... Dec 2023The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the...
PURPOSE
The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the pathogenic elements of AMD resemble those of autoimmune diseases, yet the association between AMD development and most autoimmune diseases remain unexplored.
METHODS
We conducted a case-control analysis of patients ages 55 and older with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD between 2005 and 2019 in the Merative MarketScan Commercial and Medicare Databases. The diagnosis of an autoimmune disease was defined by an outpatient or inpatient claim with a relevant ICD code in the 12 months before the index visit. Conditional multivariable logistic regression, adjusted for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals.
RESULTS
We identified 415,027 cases with new-onset ICD coding for AMD matched with propensity scores to 414,853 controls. In total, 16.1% of cases and 15.9% of controls were diagnosed with any autoimmune disease. The diagnosis of any autoimmune disease did not affect the odds of new-onset ICD coding for AMD in multivariable regression (OR = 1.01; 95% CI, 0.999-1.02). Discoid lupus erythematosus (OR = 1.29; 95% CI, 1.12-1.48), systemic lupus erythematosus (SLE) (OR = 1.21; 95% CI, 1.15-1.27), giant cell arteritis (OR = 1.19; 95% CI, 1.09-1.30), Sjogren's syndrome (OR = 1.17; 95% CI, 1.09-1.26), and Crohn's disease (OR = 1.13; 95% CI, 1.06-1.22) increased the odds of a new-onset ICD coding for AMD.
CONCLUSIONS
Most autoimmune diseases do not affect the odds of developing AMD but several common autoimmune disorders such as SLE and Crohn's disease were associated with modestly increased odds of AMD. Further studies are needed to validate and investigate the underlying mechanisms of these associations.
Topics: United States; Humans; Aged; Crohn Disease; Medicare; Autoimmune Diseases; Lupus Erythematosus, Systemic; Macular Degeneration
PubMed: 38153747
DOI: 10.1167/iovs.64.15.45