Treatment Of Autoimmune Diseases Research Articles

Single-Cell Sequencing: High-Resolution Analysis of Cellular Heterogeneity in Autoimmune Diseases.

Autoimmune diseases (AIDs) are complex in etiology and diverse in classification but clinically show similar symptoms such as joint pain and skin problems. As a result, the diagnosis is challenging, and usually, only broad treatments can be available. Consequently, the clinical responses in patients with different types of AIDs are unsatisfactory. Therefore, it is necessary to conduct more research to figure out the pathogenesis and therapeutic targets of AIDs. This requires research technologies with strong extraction and prediction capabilities. Single-cell sequencing technology analyses the genomic, epigenomic, or transcriptomic information at the single-cell level. It can define different cell types and states in greater detail, further revealing the molecular mechanisms that drive disease progression. These advantages enable cell biology research to achieve an unprecedented resolution and scale, bringing a whole new vision to life science research. In recent years, single-cell technology especially single-cell RNA sequencing (scRNA-seq) has been widely used in various disease research. In this paper, we present the innovations and applications of single-cell sequencing in the medical field and focus on the application contributing to the differential diagnosis and precise treatment of AIDs. Despite some limitations, single-cell sequencing has a wide range of applications in AIDs. We finally present a prospect for the development of single-cell sequencing. These ideas may provide some inspiration for subsequent research.

Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors.

Hepatitis B reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. We conducted a SLR (PubMed, Scopus and EMBASE) and metanalysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. Overall, our study revealed a low HBVr risk of < 6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14,4% vs 5.1%, respectively p< 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis the respective percentage was 4.7%. Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.

Discovery of KT-474─a Potent, Selective, and Orally Bioavailable IRAK4 Degrader for the Treatment of Autoimmune Diseases.

Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential mediator of the IL-1R and TLR signaling pathways, both of which have been implicated in multiple autoimmune conditions. Hence, blocking the activity of IRAK4 represents an attractive approach for the treatment of autoimmune diseases. The activity of this serine/threonine kinase is dependent on its kinase and scaffolding activities; thus, degradation represents a potentially superior approach to inhibition. Herein, we detail the exploration of structure-activity relationships that ultimately led to the identification of KT-474, a potent, selective, and orally bioavailable heterobifunctional IRAK4 degrader. This represents the first heterobifunctional degrader evaluated in a nononcology indication and dosed to healthy human volunteers. This molecule successfully completed phase I studies in healthy adult volunteers and patients with atopic dermatitis or hidradenitis suppurativa. Phase II clinical trials in both of these indications have been initiated.

Autocrine VEGF-B signaling maintains lipid synthesis and mitochondrial fitness to support T cell immune responses.

T cells rewire their metabolic activities to meet the demand of immune responses, but how to coordinate the immune response by metabolic regulators in activated T cells is unknown. Here, we identified autocrine VEGF-B as a metabolic regulator to control lipid synthesis and maintain the integrity of the mitochondrial inner membrane for the survival of activated T cells. Disruption of autocrine VEGF-B signaling in T cells reduced cardiolipin mass, resulting in mitochondrial damage, with increased apoptosis and reduced memory development. The addition of cardiolipin or modulating VEGF-B signaling improved T cell mitochondrial fitness and survival. Autocrine VEGF-B signaling through GA-binding protein α (GABPα) induced sentrin/SUMO-specific protease 2 (SENP2) expression, which further de-SUMOylated PPARγ and enhanced phospholipid synthesis, leading to a cardiolipin increase in activated T cells. These data suggest that autocrine VEGF-B mediates a signal to coordinate lipid synthesis and mitochondrial fitness with T cell activation for survival and immune response. Moreover, autocrine VEGF-B signaling in T cells provides a therapeutic target against infection and tumors as well as an avenue for the treatment of autoimmune diseases.

Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics

Due to its stimulatory potential for immunomodulatory CD4+ regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of invivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38+, skin-homing HLA-DR+, and highly proliferative inflammation-homing CD38+ HLA-DR+ Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.

Discovery of ICOS-targeted small molecules using affinity selection mass spectrometry screening.

Inducible T cell co-stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS-L). Although clinical benefits have been reported in the ICOS modulation-based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS-targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules. To the best of our knowledge, this is the first study that utilizes ASMS screening to discover small molecules targeting immune checkpoints. Compound 9 with a promising ICOS/ICOS-L inhibitory profile (IC 50 = 29.38 ± 3.41 µM) was selected as the template for the modification. Following preliminary structure-activity relationship (SAR) study and molecular dynamic (MD) simulation revealed the critical role of the ortho-hydroxy group on compound 9 in the ICOS binding, as it could stabilize the interaction via the hydrogen bond formation with residuals on the glycan, and the depletion could lead to an activity lost. This work validates a promising inhibitor for the ICOS/ICOS-L interaction, and we anticipate future modifications could provide more potent modulators for this interaction.

Adverse Event Profiles of Adalimumab in Children: A Disproportionality Analysis.

Adalimumab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult rheumatoid arthritis (RA), and subsequently approved for pediatric treatment of various autoimmune diseases in children of different ages. Due to genetic differences between children and adults in terms of physiology and immunity, there is a need to explore the safety of adalimumab in children in the real world. The aim of this study is to identify potential adverse event (AE) signals associated with the use of adalimumab in pediatric patients (<18 years old) using data from the FDA Adverse Event Reporting System (FAERS). AEs associated with adalimumab in pediatric patients reported in the FAERS database from the first quarter (Q1) of 2017 to the third quarter (Q3) of 2022 were systematically gathered. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayes geometric mean (EBGM) were used to assess the relationship between adalimumab and AEs in children. Out of 8,363,304 reports collected from the FAERS database during the study period, 3819 reports on children on adalimumab were identified. Adalimumab-related AEs reports were concentrated on 10 toxicity areas and a total of 202 positive signals were detected, of which injection site papule (ROR = 261.97) and intestinal fistula (ROR = 122.09) had the strongest signals. Unexpected significant AEs, including intestinal obstruction, immunodeficiency, abdominal abscess, and Takayasu's arteritis might also occur. In comparison with patients of all ages in the same time window, the median onset time of children was shorter (99 vs. 149 days). Most of the AE cases occurred in children within the first 1 (1.71%), 2 (8.12%), and 3 months (8.39%) and had early failure types after adalimumab initiation. Methotrexate, folic acid, prednisone, azathioprine, and mesalamine were the top five drugs used concomitantly for adalimumab-associated AEs. When adalimumab is used in children, especially in the first 3 months of treatment, in addition to the AEs recorded in the drug package insert, close attention should be paid to the new potential AEs off-label to ensure the safety of adalimumab in children.

Yiqi Jiedu Xiaoying Decoction Improves Experimental Autoimmune Thyroiditis in Rats by Regulating Th17/Treg Cell Balance.

Experimental autoimmune thyroiditis (EAT) is a widely used animal model to study the pathogenesis and treatment of autoimmune thyroid diseases. Yiqi Jiedu Xiaoying Decoction (YJXD) is a traditional Chinese medicine formula with potential immunomodulatory effects. In this study, we investigated the therapeutic effects of YJXD on EAT in rats and explored its underlying mechanisms. Female Wistar rats were induced to develop EAT by immunization with thyroglobulin (Tg) and taken sodium iodide water (0.05%) and then treated with YJXD or sodium selenite. HE staining was used to observe the pathological changes of thyroid tissue in EAT rats. Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expression levels of Th17- and Treg-related cytokines and thyroid autoantibody were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Th17- and Treg-related transcriptional factors was detected by real-time polymerase chain reaction (RT-PCR) and Immunohistochemistry (IHC). Our results demonstrated that treatment with YJXD significantly attenuated the severity of EAT, as evidenced by reduced thyroid gland inflammatory infiltration and decreased serum thyroglobulin autoantibody levels. Importantly, YJXD treatment effectively modulated the Th17/Treg cell balance by suppressing Th17 cell differentiation and promoting Treg cell expansion. Moreover, YJXD was also found to regulate the expression levels of Th17- and Treg-related cytokines and transcriptional factors, further supporting its immunomodulatory effects in EAT. YJXD exerted therapeutic effects on EAT by regulating the Th17/Treg cell balance, modulating the production of Th17- and Treg-related cytokines and the expression of transcriptional factors.

Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.

Regulatory T cells (Tregs), characterized by the expression of Forkhead Box P3 (FOXP3), constitute a distinct subset of T cells crucial for immune regulation. Tregs can exert direct and indirect control over immune homeostasis by releasing inhibitory factors or differentiating into Th-like Treg (Th-Treg), thereby actively contributing to the prevention and treatment of autoimmune diseases. The epigenetic regulation of FOXP3, encompassing DNA methylation, histone modifications, and post-translational modifications, governs the development and optimal suppressive function of Tregs. In addition, Tregs can also possess the ability to maintain homeostasis in diverse microenvironments through non-suppressive mechanisms. In this review, we primarily focus on elucidating the epigenetic regulation of Tregs as well as their multifaceted roles within diverse physiological contexts while looking forward to potential strategies involving augmentation or suppression of Tregs activity for disease management, particularly in light of the ongoing global COVID-19 pandemic.

Pyroptotic-Spatiotemporally Selective Delivery of siRNA against Pyroptosis and Autoimmune Diseases.

Small-interfering RNAs (siRNAs) offer promising prospects for treating pyroptosis-related autoimmune diseases. However, poor stability and off-target effects during in vivo transportation hinder their practical clinical applications. Precision delivery and adaptive release of siRNAs into inflamed tissues and immune cells could unleash their full therapeutic potential. This study establishes a pyroptotic-spatiotemporally selective siRNA delivery system (PMRC@siGSDME) that selectively targets inflammatory tissues, responds to pyroptosis, and exhibits remarkable therapeutic efficacy against various autoimmune diseases. Novel hybrid nanovesicles (NVs) are designed as a combination of pyroptotic macrophage membranes (PMs) and R8-cardiolipin-containing nanovesicles (RC-NVs). Evidence provides that PM-derived proteins involved in cell-cell interactions and membrane trafficking may contribute to the specificity of NVs to inflammatory tissue. In addition, cardiolipin anchored in the hybrid NVs increases its affinity for activated gasdermin E (GSDME) and achieves pyroptosis-adaptive release of siGSDME for the spatiotemporally selective suppression of immune responses. More importantly, PMRC@siGSDME displays significant anti-inflammatory and therapeutic effects in multiple mouse autoimmune disease models, including arthritis and inflammatory bowel disease (IBD). Collectively, an innovative siRNA delivery strategy precisely tailored for pyroptotic cells has been developed, paving the way for new treatments for autoimmune inflammatory diseases with minimal side effects and wide clinical applicability.

Interdisciplinary centers for autoimmune diseases in Germany

Interdisciplinary medical treatment is required to care for patients with complex autoimmune diseases. Although there are an increasing number of interdisciplinary centers for autoimmune diseases in Germany, they are not yet available throughout the country and the focuses and interdisciplinary structures are not organized according to agenerally agreed standard. Furthermore, they are not regularly reflected in the general care structure. To analyze the care structure using as an example an established center and aclinical case to demonstrate the usefulness of in-house standardized procedures. In order to determine the status quo regarding interdisciplinary centers for autoimmune diseases in Germany, a university hospital is exemplarily presented for astructural analysis and acase presentation from another center to demonstrate the importance of an interdisciplinary patient care. At the selected center for autoimmune diseases of the university hospital, patients with autoimmune diseases receive interdisciplinary care from experts from various disciplines. The structures are anchored in an organizational chart. The case report demonstrates astandardized diagnostic and therapeutic pathway (standardized operating procedures, SOP) in apatient with systemic sclerosis and lung involvement. The article discusses which measures are necessary across disciplines for comprehensive diagnostics and treatment of certain autoimmune diseases, which challenges arise during implementation and which advantages can arise compared to guidelines because, among other things, they can be immediately adapted. The establishment of anational consensus for the structure, necessary settings and implementation into patient care within an interdisciplinary center for autoimmune diseases is desirable.

Progress of monoclonal antibodies in the treatment of autoimmune diseases

Progress of monoclonal antibodies in the treatment of autoimmune diseases

Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.

Lck, a member of the Src kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance the cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibiting tyrosine kinases has been a highly successful approach to treating hematologic malignancies. The inhibitors may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown interesting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs. host disease. Drug repurposing and bioinformatics can aid in solving several unsolved issues about the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

Methods of Prevention and Mitigation of Autoimmune Diseases - A Review of The Literature

Introduction and purpose: Autoimmune diseases are conditions where the body’s immune system is unable to distinguish between auto- and foreign antigens and mistakenly attacks its cells, tissues, and organs. In recent years it became major public health concern because of the increasing diagnosis rate. Currently, about 5% of the population in Western countries is affected by such diseases, more often in women population. The exact cause of autoimmune diseases is unknown, although most probably it results from a combination of genetic predisposition, environmental risk factors and immune dysregulation. Development of autoantigen-specific lymphocytes and autoantibodies might be decisive in starting the process of autoimmunity. Most common medication used in autoimmune diseases treatment are nonsteroidal anti-inflammatory drugs (NSADs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs). Additionally, there is biological medication available for many of them. It is known that non-pharmacological interventions, such as specific diets, supplementation or physical exercise is useful to mitigate the disease or even to prevent the body from its onset. Materials and methods: The data for the article was found using the PubMed and Google Scholar websites. The key words used for the search included: ‘diet and autoimmunity’, ‘autoimmunity and estrogens’, ‘microbiota and autoimmunity’. Articles not written in English, conference abstracts only and duplicated papers were excluded. Conclusions: There is still no cure for autoimmune diseases, although various prevention and mitigation strategies can help manage these conditions and improve quality of life for affected individuals. However, for the use of some of them, evidence-based recommendations are not available. This review highlights current non-pharmacological therapeutic options.

ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.

Endoplasmic reticulum aminopeptidases ERAP1 and 2 are intracellular aminopeptidases that trim antigenic precursors and generate antigens presented by major histocompatibility complex class I (MHC-I) molecules. They thus modulate the antigenic repertoire and drive the adaptive immune response. ERAPs are considered as emerging targets for precision immuno-oncology or for the treatment of autoimmune diseases, in particular MHC-I-opathies. This perspective covers the structural and biological characterization of ERAP, their relevance to these diseases and the ongoing research on small-molecule inhibitors. We describe the chemical and pharmacological space explored by medicinal chemists to exploit the potential of these targets given their localization, biological functions, and family depth. Specific emphasis is put on the binding mode, potency, selectivity, and physchem properties of inhibitors featuring diverse scaffolds. The discussion provides valuable insights for the future development of ERAP inhibitors and analysis of persisting challenges for the translation for clinical applications.

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis.

Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases. In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo. The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos. For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.

Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

Advances in glucocorticoid resistance in otorhinolaryngological diseases

Glucocorticoids（GC） are widely used in the clinical treatment of autoimmune inner ear diseases, sudden sensorineural hearing loss, Meniere's disease, sinusitis and other otolaryngology diseases. However, GC resistance remains a major factor contributing to the poor efficacy of clinical treatments. The mechanism of GC resistance is still unclear. This paper reviews the related mechanisms of GC resistance from the perspectives of GC receptor factors and non-GC receptor factors. Additionally, it summarizes the latest research progress on GC resistance in otolaryngological diseases, with the aim of identifying effective clinical alternative treatment options for reversing GC resistance in the future.

Cell-drug conjugates.

By combining living cells with therapeutics, cell-drug conjugates can potentiate the functions of both components, particularly for applications in drug delivery and therapy. The conjugates can be designed to persist in the bloodstream, undergo chemotaxis, evade surveillance by the immune system, proliferate, or maintain or transform their cellular phenotypes. In this Review, we discuss strategies for the design of cell-drug conjugates with specific functions, the techniques for their preparation, and their applications in the treatment of cancers, autoimmune diseases and other pathologies. We also discuss the translational challenges and opportunities of this class of drug-delivery systems and therapeutics.

Autophagy, apoptosis, and inflammation response of Sebastiscus marmoratus to different concentrations of hydroxychloroquine

Hydroxychloroquine (HCQ) is an important public health therapeutic agent widely used in the prevention and treatment of malaria and autoimmune diseases, with some antiviral effects, as well as a common autophagy inhibitor. Its autophagy-inhibiting effect attracts great research interest in mammals but is still little studied in fish. We even have no idea about the effects of HCQ on different tissues of fish and what concentrations should be used for safety studies. This study investigated the effect of different concentration of HCQ treatments on the survival, tissue structure, and expressions of genes related to autophagy, apoptosis, and inflammation in the gill, spleen, testis, and ovary of Sebastiscus marmoratus. The results showed that the higher HCQ concentration (77.40 and 154.80 mg/mL) led to mass mortality within an hour. The half-lethal concentration (LC50, 24 h) of HCQ for S. marmoratus was approximately 48.95 mg/mL. When exposed to 30.96 mg/mL HCQ for 24 hours, autophagy was blocked as revealed by electron microscopy from gill, spleen and testis of fish. The expressions of autophagy-related genes (LC3/Cx43), apoptosis-related genes (Cas3/p53), and inflammation-related genes (TNF-α/IL8) exhibited tissue-specific and dose-dependent responses. The gonads showed preferential expression of all these genes and were found to be sensitive and regular after HCQ treatment. For example, at a concentration of 30.96 mg/mL, the testis demonstrated a regularity that suggests it is an ideal candidate tissue for studying the role of HCQ or autophagy. This study systematically revealed the response of S. marmoratus to different concentrations of HCQ and provided optional assay concentrations for key tissues, serving as an important reference for the future studies on HCQ and autophagy in S. marmoratus. Furthermore, the potential crosstalk between autophagy, apoptosis, and inflammatory pathways initially identified in this study could be helpful for the future research on autophagy regulation in marine fish.