Mitochondria serve as the powerhouses of living cells, supplying energy and essential building blocks for cellular activities. The immune system exhibits a dynamic and active characteristic within the body, wherein immune cells are constantly activated and primed for pathogens without causing harmful effects on the self-body. These characteristics necessitate that immune cells function effectively and correctly, supported by a sufficient energy supply and metabolism from the mitochondria. Mitochondrial dysfunction leads to immune dysregulation, resulting in inappropriate inflammation, autoimmunity, immunodeficiency, and hypersensitive responses, all of which contribute to the development of illness and disease. Recent studies on mitochondrial transfer in immune cells indicate that mitochondrial replacement could emerge as a promising tool for rectifying immune cell function. This review will emphasize the role of mitochondria in various immune cell types and explore how mitochondrial dysfunction can result in pathogenesis in different conditions. We also discuss the potential application of mitochondrial transfer and transplantation to- and from immune cells in the context of health and disease.

Extracellular vesicles (EVs), nano-sized particles enclosed by a lipid membrane, play a pivotal role in cell-to-cell communication as essential mediators in various biological processes and diseases. Despite their ability to interact with multiple targets, EVs notably demonstrate a high affinity for specialized cells within the extracellular environment, particularly mononuclear phagocytes. The interaction between EVs and mononuclear phagocytes significantly affects the profile of these cells. Several factors, including vesicle cargo, size, parental cell origin, involved receptors, and the specific endocytic pathway, influence EVs' consequences and subsequent responses. Key components of mononuclear phagocytes, monocytes and macrophages, play a crucial role in the innate immune system, contributing to tissue damage, repair, remodeling, inflammation, homeostasis maintenance, and disease progression. Despite extensive research on EVs in various health and disease contexts, their precise impact on mononuclear phagocytes remains incompletely understood. Therefore, this review explores EVs' role in modulating monocyte and macrophage profiles and functions across different scenarios. It emphasizes that EVs actively shape the phenotype of these mononuclear phagocytes to maintain homeostasis and regulatory functions, but also induce pro-inflammatory polarization in infectious diseases, systemic inflammation, and autoimmunity. Simultaneously, during neoplastic or tumor development, the EV-mononuclear phagocyte axis prompts imbalanced responses, combining pro- and anti-inflammatory outcomes. These findings confirm EVs as promising tools for therapeutic strategies to modulate mononuclear phagocyte functions in diverse pathological settings.

Inflammatory bowel disease (IBD) varies in prevalence globally. Recent rise in IBD cases mirrors evolving health landscape due to urbanization and lifestyle changes worldwide. Existing drugs for IBD include aminosalicylates, corticosteroids, Immunomodulators, biologics, JAK inhibitors, and antibiotics. Although these medications are effective in managing symptoms and remission, these present several with limitations. Side effects such as nausea, infections, and liver toxicity are common, and some patients may develop resistance or lose response over time. Additionally, biologics can be costly, and immunosuppressive drugs raise concerns about long-term safety along increased risk of infection. Importantly, approximately 10% to 30% of the IBD patients do not respond to conventional treatments such as corticosteroids, immunosuppressants, or biologic therapies. Research continues to explore new treatments to address these limitations and improve outcomes for individuals with IBD. This review is an attempt to critically evaluate the currently available treatments for IBD underlining their limitations, and the pressing demand for innovative strategies. Further, we delve into the rationale behind peptide-based therapies, emphasizing their potential to modulate inflammation and promote mucosal healing. The work also highlights promising outcomes from recent preclinical and clinical studies underscoring the pivotal role of peptides in IBD management.

Despite advancements in breast cancer treatment, therapeutic resistance, and tumor recurrence continue to pose formidable challenges. Therefore, a deep knowledge of the intricate interplay between the tumor and the immune system is necessary. In the pursuit of combating breast cancer, the awakening of antitumor immunity has been proposed as a compelling avenue. Tumor stroma in breast cancers contains multiple stromal and immune cells that impact the resistance to therapy and also the expansion of malignant cells. Activating or repressing these stromal and immune cells, as well as their secretions can be proposed for exhausting resistance mechanisms and repressing tumor growth. NK cells and T lymphocytes are the prominent components of breast tumor immunity that can be triggered by adjuvants for eradicating malignant cells. However, stromal cells like endothelial and fibroblast cells, as well as some immune suppressive cells, consisting of premature myeloid cells, and some subsets of macrophages and CD4+ T lymphocytes, can dampen antitumor immunity in favor of breast tumor growth and therapy resistance. This review article aims to research the prospect of harnessing the power of drugs, adjuvants, and nanoparticles in awakening the immune reactions against breast malignant cells. By investigating the immunomodulatory properties of pharmacological agents and the synergistic effects of adjuvants, this review seeks to uncover the mechanisms through which antitumor immunity can be triggered. Moreover, the current review delineates the challenges and opportunities in the translational journey from bench to bedside.

Studies in murine experimental models have made significant contributions to the understanding of asthma pathophysiology and the discovery of innovative therapeutic approaches. Nonetheless, there is a plethora of options available for selecting mouse strains, sensitization methods, challenge routes and doses, as well as approaches to evaluating host response in murine asthma model protocols. Due to the diversity of models employed, comparing results across different studies proves exceedingly challenging. The study conducted a search of pertinent PubMed articles from 2022 to April 15th, 2024. After relevant publications had been selected, the characteristics of each study were extracted, including animal strains, animal sex, sensitization methods, challenge methods, and reported outcome measures. The modeling parameters of Ovalbumin (OVA)-induced asthma model, and House Dust Mite-induced asthma model were analyzed. Additionally, we extracted data on the dose of OVA sensitization, alum administration, challenge OVA dose, and alum/sensitization OVA ratio from seven included studies. Subsequently, we conducted an analysis to determine the correlation between each of these factors and the lung resistance index (RI). This study presents an overview of the current mouse asthma models, offering valuable methodological guidance for researchers. Furthermore, this study highlights that certain parameters like sensitization dose, challenge dose, and so on, exert specific effects on the asthma lung resistance. However, there is a lack of standardized criteria and guidelines in this regard. The effects and underlying mechanisms of parameters on asthma responses remain unclear, necessitating further investigation into model parameters.

T cells play a crucial role in immune responses and are involved in chronic diseases such as Type 2 Diabetes Mellitus (T2DM) and its complications, including Diabetic Nephropathy (DN). Among these, regulatory T cells (Treg) act as key regulators, while T helper 9 (Th9) cells, which produce IL-9, are essential in maintaining immune balance.

Preventive vaccination is a crucial strategy for controlling and preventing infectious diseases, offering both effectiveness and cost-efficiency. However, despite the widespread success of vaccination programs, there are still certain population groups who struggle to mount adequate responses to immunization. These at-risk groups include but are not restricted to the elderly, overweight individuals, individuals with chronic infections and cancer patients. All of these groups are characterized by persistent chronic inflammation. Recent studies have demonstrated that one of the key players in immune regulation and the promotion of chronic inflammation are myeloid-derived suppressor cells (MDSCs). These cells possess a wide range of immunosuppressive mechanisms and are able to dampen immune responses in both antigen-specific and antigen-nonspecific manner, thus contributing to the establishment and maintenance of an inflammatory environment. Given their pivotal role in immune modulation, there is growing interest in understanding how MDSCs may influence the efficacy of vaccines, particularly in vulnerable populations. In this narrative review, we discuss whether MDSCs are able to regulate vaccine-induced immunity and whether their suppression can potentially enhance vaccine efficacy in vulnerable populations.

Host immunity helps the body to fight against COVID-19. Single-cell transcriptomics has provided the scope of investigating cellular and molecular underpinnings of host immune response against SARS-CoV-2 infection at high resolution. In this review, we have systematically described the virus-induced dysregulation of relative abundance as well as molecular behavior of each innate and adaptive immune cell type and cell state during COVID-19 infection and for different vaccinations, based on single-cell studies published in last three-four years. Identification and characterization of these disease-associated specific cell populations might help to design better, efficient, and targeted therapeutic avenues.

Macrophages are the primary targets of mycobacterial infection, which plays crucial roles both in nonspecific defence (innate immunity) as well as specific defence mechanisms (adaptive immunity) by secreting various cytokines, antimicrobial mediators and presenting antigens to T-cells. Sequencing of the mycobacterial genome revealed that 10% of its coding ability is devoted to the Pro-Glu motif-containing (PE) and Pro-Pro-Glu motif-containing (PPE) family proteins. While the function of most of the genes belonging to the PE-PPE family initially remained unannotated, recent studies have shown that many proteins of this family play critical roles in bacterial growth and cell functions, and manipulation of host immune responses, indicating their potential roles in mycobacterial virulence. In this review, we have focussed on describing the immunological importance of particularly the PE group of proteins in the context of 'virulence' determinants and outcome of tuberculosis disease. Additionally, we have discussed about the roles of these proteins on host-pathogen-interaction and how some of these genes can be targeted which may help us in designing effective anti-TB therapeutics.

Heart failure (HF) causes structural and functional changes in the heart, with the pyroptosis-mediated inflammatory response as the core link in HF pathogenesis. E3 ubiquitin ligases participate in cardiovascular disease progression. Here, we explored the underlying molecular mechanisms of E3 ubiquitin ligase Smurf1 in governing HF.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by excessive production of type I interferons (IFNs) and autoantibodies with limited effective clinical treatments. Solute carrier family 15 member 4 (SLC15A4), a proton-coupled oligopeptide transporter, facilitates the transmembrane transport of L-histidine and some di- and tripeptides from the lysosome to the cytosol. A growing body of evidence has elucidated the critical role of SLC15A4 in pathogenesis and disease progression of SLE. Genome-wide association studies have identified SLC15A4 as a new susceptibility locus of SLE. Further mechanistical studies have demonstrated that SLC15A4 involves in the production of type I IFNs in plasmacytoid dendritic cells (pDCs) and its necessity in B cells for autoantibody production in lupus models. These studies strongly support the potential of SLC15A4 as a promising therapeutic target for SLE. This review aims to summarize recent advances in understanding the role of SLC15A4 in disease progression of SLE and the development of SLC15A4-targeted inhibitors as well as discuss its potential as a target for SLE treatment.

Innate lymphoid cells (ILCs) have emerged as pivotal players in the field of immunology, expanding our understanding of innate immunity beyond conventional paradigms. This comprehensive review delves into the multifaceted world of ILCs, beginning with their serendipitous discovery and traversing their ontogeny and heterogeneity. We explore the distinct subsets of ILCs unraveling their intriguing plasticity, which adds a layer of complexity to their functional repertoire. As we journey through the functional activities of ILCs, we address their role in immune responses against various infections, categorizing their interactions with helminthic parasites, bacterial pathogens, fungal infections, and viral invaders. Notably, this review offers a detailed examination of ILCs in the context of specific infections, such as , , , , , , , , , Cytomegalovirus, Herpes simplex virus, and severe acute respiratory syndrome coronavirus 2. This selection aimed for a comprehensive exploration of ILCs in various infectious contexts, opting for microorganisms based on extensive research findings rather than considerations of virulence or emergence. Furthermore, we raise intriguing questions about the potential immune functional resemblances between ILCs and epithelial cells, shedding light on their interconnectedness within the mucosal microenvironment. The review culminates in a critical assessment of the therapeutic prospects of targeting ILCs during infection, emphasizing their promise as novel immunotherapeutic targets. Nevertheless, due to their recent discovery and evolving understanding, effectively manipulating ILCs is challenging. Ensuring specificity and safety while evaluating long-term effects in clinical settings will be crucial.

Membranous nephropathy (MN), an autoimmune cause of adult nephrotic syndrome, is driven by podocyte-targeting antibodies against PLA2R/THSD7A. Current models fail to fully capture human disease progression. This review evaluates three transformative approaches: (1) Heterologous antibody-induced models enabling acute injury replication; (2) Antigen-driven immunization modeling adaptive immunity; and (3) GBF-on-Chip platforms mimicking filtration barrier dynamics. Collectively, they reveal complement-dependent and direct podocytotoxic injury mechanisms. While antibody-induced models offer rapid injury induction and high reproducibility, their transient phenotype cannot model chronic progression or immune tolerance breakdown. Antigen-driven models recapitulate adaptive immunity but face prolonged timelines and epitope targeting bias diverging from human IgG4 dominance. GFB-on-Chip systems excel in mechanistic dissection of podocyte injury but lack immune microenvironment integration and physiologically accurate glomerular architecture. This review synthesizes strategies for MN model development through antibody-podocyte interaction studies, critically evaluates the strengths of existing platforms, and discusses emerging technologies for probing disease mechanisms and accelerating therapeutic discovery.

B-cells are vital immune cells that differentiate into plasma cells to produce antibodies targeting specific antigens. They also act as Antigen Presenting Cells, displaying processed antigens on Major Histocompatibility Complex class-II molecules to activate helper T-cells. This process triggers immune response and memory development. B-cells have surface antigens crucial for their function, which are often overexpressed in B cell cancers, making them targets for therapies like Chimeric Antigen Receptor (CAR) T-cell therapy. However, the choice of antigen is crucial. Tumor associated antigens are common but can cause off-target effects, while tumor specific antigens are more specific but less common. Furthermore, the precise epitope on the antigen recognized by the CAR-T cells significantly influences activation, which can also depend on the epitope's distance from the B-cell membrane. To facilitate the identification of extracellular regions of tumor antigens for CAR interactions, this review models tumor antigen structures embedded in the lipid bilayer, analyzing their roles and functions. Specifically, the characterization of B-cell surface antigens, encompassing their structural features and their potential as targets for CAR-T therapy are discussed. Each antigen is meticulously examined to gain insights into their specific roles within B cell biology and their potential as therapeutic targets. In conclusion, this review highlights the importance of understanding B cell antigens for the development of effective CAR-T cell therapies. The insights into antigen structures and functions presented here can guide the selection of optimal targets and the design of CAR-T cells to combat B cell malignancies effectively.

The livers' ability to regenerate after injury has attracted the investigation of possible therapeutic targets for liver disease. Cells of the immune system are considered fundamental for the initiation, propagation, and termination of liver regeneration as they produce essential signaling molecules, such as cytokines, chemokines, and growth factors. Previous evidence mainly focused on macrophage involvement in liver regeneration, namely Kupffer cells which secrete mitogenic cytokines. However, recent evidence has implicated other immune cell subsets in liver regeneration including platelets, the complement system, dendritic cells, granulocytes, and innate and adaptive lymphocytes. The concurrent function of different immune cell subsets highlights functional redundancies between immune cells and the temporospatial dynamics of liver regeneration. In this review, we discuss our understanding of the role of immune cells in liver regeneration, recent advances and cellular targets identified for clinical therapy over the past decade.

() employs diverse virulence factors to evade immune defenses and persist intracellularly. The ESAT-6 secretion system-1 (ESX-1) type VII secretion system (T7SS) releases EsxA, EspA, and EspB, inducing phagosomal rupture and cytosolic access while triggering host defenses, including galectin recruitment and stress granule formation. To counteract host responses, utilizes phthiocerol dimycocerosates (PDIMs) to inhibit autophagy and LC3-associated phagocytosis (LAP) by suppressing NADPH oxidase (NOX2) recruitment and reactive oxygen species (ROS) production. Additionally, CspA blocks LC3 lipidation, impairing LAP activation and phagosome maturation. EsxG and EsxH interfere with ESCRT-mediated phagosomal repair, further enhancing intracellular survival. Cytosolic is ubiquitinated by host E3 ligases, marking it for selective autophagy (xenophagy), yet evades degradation by manipulating autophagic flux. Simultaneously, -derived DNA activates the cyclic GMP-AMP synthase-stimulator of interferon response cGAMP interactor 1 (CGAS-STING1) axis, leading to type I interferon (IFN) signaling and inflammasome activation, which drive IL-1B and IL-18 secretion, necrosis, and pyroptosis, facilitating bacterial dissemination. Additionally, exosomes released during infection disseminate bacterial components, modulating immune responses systemically. This review uniquely integrates current findings on the coordinated actions of ESX-1 T7SS and PDIMs in mediating phagosomal rupture and immune evasion, offering a unified framework for understanding 's intracellular survival strategies. By bridging lipid- and protein-mediated virulence mechanisms and their impact on host autophagy, inflammasome activation, and phagosomal repair pathways, this work provides novel insights into therapeutic targets aimed at restoring host immune function.

Granulomatosis with polyangiitis (GPA) is an autoimmune condition. This study evaluated the relationship between gene polymorphisms, specifically rs231775, rs5742909, and rs3087243, and the risk of developing GPA.

Antibody-drug conjugates (ADCs) are produced by integrating the specificity of monoclonal antibodies with cytotoxic payloads. ADCs are vital biologics for breast cancer treatment where they not only exert direct cytotoxicity but also promote anti-tumor immune responses against breast cancers. In this review, the structure, mechanism of action, and the anti-tumor immune response properties of approved and emerging ADCs are presented and discussed. The FDA-approved ADCs include trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG-Trop2), and trastuzumab deruxtecan (T-DXd), as well as two emerging ADCs, i.e. datopotamab deruxtecan (Dato-DXd) and ladiratuzumab vedotin (LV). Preclinical and clinical studies demonstrate their efficacy in multiple breast cancer subtypes (e.g. HER2 and triple negative breast cancers). These ADCs exert anti-tumor activity through cytotoxic effects and immune responses primarily by recruiting and activating cytotoxic T cells. Moreover, combining ADCs with immune checkpoint inhibitors (ICIs) shows enhanced therapeutic outcomes. ADCs resistance is caused by heterogeneous target antigens expression, modified ADC processing including endocytosis and lysosomal trafficking, as well as upregulated drug-efflux pumps that decrease payload concentration intracellularly. Strategies to mitigate ADCs resistance include multi-target ADCs, and stability-enhancing linkers that also reduce off-target toxicities. ADCs continue to play key roles in breast cancer treatment, while next-generation ADCs may address current ADCs' limitations and resistance mechanisms.

Atheroma formation is initiated by the activation of endothelial and smooth muscle cells, as well as immune cells, including neutrophils, lymphocytes, monocytes, macrophages, and dendritic cells. Monocytes, macrophages, and neutrophils are the innate immune cells that provide a rapid initial line of defence against vascular disease. These cells have a short lifespan and cannot retain memories, making them potential therapeutic targets for the inflammatory process associated with atherosclerosis. In addition, macrophages comprise the majority of vessel wall infiltrates and are, therefore, implicated in all stages of atherosclerosis progression. Neutrophils are the most common type of leukocyte found in circulation, and their high levels of matrix-degrading protease explain their significance in fibrous cap destabilization. However, the activation of immune cells becomes more complex by various microenvironmental stimuli and cytokines, which ultimately transform immune cells into their pro-inflammatory state. Different types of macrophage subsets with distinct functions in inflammation, such as M1 macrophages, cause an increase in pro-inflammatory cytokines and produce reactive oxygen species and nitric oxide, further worsening the disease. This review aims to shed light on immune-mediated inflammation in cardiovascular disease by focusing on the role of macrophage subsets in vascular inflammation and plaque stability, as well as the interaction between neutrophils and monocyte-macrophages.