Cellular microbiology has recently been described as a new discipline emerging at the interface between cell biology and microbiology (Cossart et al., 1996). Many microbial pathogens can enter eukaryotic cells and live intracellularly either inside vacuoles or in the cytoplasm. The different steps during the invasion process are on the way of being dissected at the molecular level revealing new insights in basic cellular functions. Indeed, bacterial pathogenesis can help us to better understand the dynamics of cell cytoskeleton, intracellular membrane traffic and signal transduction events. The recent advancements in the field of microbial pathogenesis are creating a new cross-talk between cell biologists, microbiologists and immunologists. In this review, the different strategies used by several pathogens are presented and the mechanisms elaborated by host cells from the immune system to eliminate the parasites discussed.
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Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae affecting the skin and peripheral nerves. Despite M. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during M. leprae infection is poorly understood. Conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and ELISA were used to study the in vitro interaction of M. leprae with the HaCaT human keratinocyte cell line. Keratinocytes uptake of M. leprae is described, and modulation of the surface expression of CD80 and CD209, cathelicidin expression and TNF-α and IL-1β production of human keratinocytes are compared with dendritic cells and macrophages during M. leprae interaction. This study demonstrated that M. leprae interaction with human keratinocytes enhanced expression of cathelicidin and greatly increased TNF-α production. The highest spontaneous expression of cathelicidin was by dendritic cells which are less susceptible to M. leprae infection. In contrast, keratinocytes displayed low spontaneous cathelicidin expression and were more susceptible to M. leprae infection than dendritic cells. The results show, for the first time, an active role for keratinocytes during infection by irradiated whole cells of M. leprae and the effect of vitamin D on this process. They also suggest that therapies which target cathelicidin modulation may provide novel approaches for treatment of leprosy.
In recent years, the global resurgence of syphilis has posed significant challenges to public health. This sexually transmitted infection, caused by the bacterium Treponema pallidum, can have severe consequences if left untreated, including neurological and cardiovascular complications. Diagnosing syphilis is complex due to its diverse clinical presentations, necessitating a multifaceted approach, including serological, molecular, and direct techniques such as dark-field microscopy. Penicillin remains the primary and effective treatment, but emerging macrolide-resistant strains have spurred investigations into alternative antibiotics. Syphilis vaccine development faces unique hurdles, yet promising strategies are under investigation. Targeted prevention strategies focus on high-risk populations such as men who have sex with men, pregnant women, and individuals with multiple sexual partners. The integration of syphilis services into primary healthcare enhances accessibility, early detection, and treatment. Innovative point-of-care diagnostics offer rapid, sensitive testing, while ongoing vaccine research holds the potential for long-term prevention. Addressing the global burden of syphilis requires a multifaceted approach, encompassing immunological advancements, innovative diagnostics, targeted prevention, and primary healthcare integration. Collaborative efforts between governments, healthcare systems, researchers, and communities are essential to effectively combat syphilis, striving toward a syphilis-free future that promotes better sexual health and overall well-being.
In recent years, investigations in immunology have led to progress in clinical medicine, including understanding transplant rejection, autoimmune diseases, immune deficiencies, inflammation, transplantation, cancer and the development of new vaccines. At a meeting recently held on the Mediterranean shore, advances in several facets of clinical immunology were the focus of discussion. Here, we highlight some of the debates that reflected advances in a variety of human immune disorders.
The 31st Annual Meeting of the American Society for Reproductive Immunology provided an excellent platform for basic and clinical scientists to brainstorm on current reproductive health issues such as repeated implantation and pregnancy failure, preterm birth, preeclampsia and genital tract infections such as HIV. The goal of the meeting was to foster cross-pollination of ideas as well as to encourage participation of young investigators in the field. The conference was preceded by the 4th Annual Post-Graduate Workshop with the theme of bringing bedside problems to the bench and facilitating collaboration between clinicians and basic scientists. Christopher Davies and Richard Bronson chaired the conference, which hosted approximately 180 delegates representing more than 26 countries across Asia, Australia, Latin America, Europe and North America.
Although tumor immunologists have been convincing themselves over the last decades that cancer can be conceived as an immunological problem—a few cells expressing novel antigens proliferate in uncontrolled fashion, in spite of the immune system’s attempts to eliminate them—they have been standing alone. Most basic cancer researchers, drug developers and clinical oncologists have been considering neoplasia as a purely cell-autonomous genetic disease and have been ignoring or even neglecting the impact of immunology on tumorigenesis, for multiple reasons. First, as a complex, multi-step disease, cancer is difficult to comprehend and even more difficult to treat, meaning that most specialists have been advocating reductionism as a strategy to “focus” on oncogenes and tumor suppressor genes as the mechanisms of tumorigenesis and on oncogene addiction (and more recently the non-oncogene addiction) as a therapeutic target. Second, driven by the consideration that cancer drugs must cure human cells, most animal models that have been used to study cancer drugs involve human cancer cell lines or primary tumor explants that are inoculated into severely immunodeficient mice. This means that any contribution of the immune system to anticancer therapy (or its failure) has been systematically overlooked during the development of cancer drugs. Third, in clinical practice, the diagnosis, prognosis or treatment of cancers has not been guided by any kind of immune parameters, including the presence of tumor-infiltrating lymphocytes or the detection of antibodies or T cells specific for tumor antigens. Fourth, many attempts to cure cancer by cytokines, adoptively transferred T cells or therapeutic vaccination have failed (at least as long according to WHO or RECIST criteria), in spite of initial successes reported in animal models, case reports or small clinical trials. Thus, until early 2010, the only FDA-approved anticancer regimens that might be considered as immunotherapies were limited to the toll-like receptor-7 agonist imiquimod for the treatment of basal and squamous cell skin cancer, as well as of genital warts (Condylomata acuminata), the cytokines interleukin-2 and interferon-〈 for the treatment of renal cell carcinoma, and Bacille Calmette-GuErin for the local treatment of superficial bladder cancer. Strikingly, the last two years have marked a turning point in the field. The FDA has approved two novel immunotherapies for the treatment of cancer, namely sipuleucel-T/PROVENGEAE, a dendritic cell-based vaccine against prostatic acid phosphatase for the treatment of advanced prostate cancer (approved in 2010), and ipilimumab/YERVOYAE, an antibody that neutralizes the T cell-inhibitory receptor CTLA-4, for the treatment of advanced melanoma (approved in 2011). Recent clinical studies suggest the clinical utility of adoptive T cell transfer and therapeutic vaccinations with gp100 plus interleukin-2 for the treatment of melanoma as well. Ongoing clinical evaluations indicate that many more immunotherapeutic approaches are in the pipeline and are very likely to reach the clinics in forthcoming years. There are a couple of additional reasons why tumor immunology is becoming an ever more popular area of research and development. First, during recent years, it has become clear that the density, composition, architecture and function of the immune infiltrate determine the prognosis of cancer patients. Moreover, it was discovered in 2010 and 2011 that the immune infiltrate also has predictive value and thus determines the likelihood that conventional anticancer therapies with cytotoxic agents will succeed in reducing tumor mass. These clinical results confirmed the research-based hypothesis that chemotherapy must stimulate an anticancer immune response in order to be successful. Accordingly, there is accumulating evidence that at least some chemotherapeutic agents can stimulate the infiltration of tumor beds by innate and cognate immune effectors. Furthermore, even the first and paradigmatic example of “targeted” cancer therapy, the tyrosine kinase inhibitor imatinib, is much more efficient in controlling the growth of cancer cells in the presence of an intact cellular immune system than in its absence. In light of the ever-accumulating evidence, the communities of researchers and clinicians, as well as the biotechnological and pharmacological industries, are now accepting a paradigm shift: cancer becomes a life-threatening disease when tumor cells escape from the control of the immune system, and successful therapies rely on the reestablishment of the equilibrium between the tumor and anticancer defense mechanisms. Novel antibodies endowed with enhanced ADCC properties are being generated by the pharmaceutical industry, while numerous biotechnology companies are engaging in the development of innovative cancer vaccines, driven by the conviction that the future standard of care of cancer will involve tailor-made combination therapies that associate immunogenic cytotoxic compounds with immunostimulatory agents and/or therapeutic vaccines. Hence, the time is ripe for this new journal, OncoImmunology, which will publish high-profile articles on all aspects of fundamental and applied tumor immunology. Aided by an Editorial Board of excellent and highly qualified researchers, OncoImmunology will publish relevant research articles, monitor important developments in the field, and provide resources to the interested research community. We thank you, readers, patients, physicians and scientists for joining us in this adventure.
Background: Inborn Errors of Immunity (IEI) are characterized by a heightened susceptibility to infections, allergies, and various other health complications. Health-Related Quality of Life (HRQOL) in patients with IEI is a critical area of research that demands attention due to the impact of IEI on patients' lives. This study utilized bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of HRQOL in patients with IEI. Methods: This bibliometric analysis utilized data from the Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) within the Web of Science core datasets up to January 1, 2024. The study focused on literature that addressed HRQOL in IEI patients, involving a total of 1,807 authors and 309 articles published across 112 journals. The analysis included publication volume and growth trends, country and institutional contributions, authorship, and journal analysis. Results: The research found that despite the importance of HRQOL in IEI, the volume of publications in this field remains consistently low, with no significant increase in trend. The USA leads in publication and citation volumes, reflecting a geographical imbalance in research contributions. Key journals in this field include the Journal of Clinical Immunology, Frontiers in Immunology, and the Journal of Allergy and Clinical Immunology. The study highlights that while treatments like hematopoietic stem cell transplants and gene therapy have improved patient IEI survival rates, they still often come with significant side effects impacting HRQOL. The analysis underlines the need for comprehensive HRQOL assessments in IEI, considering the physical and psychological impacts of treatments. Conclusions: This study represents a bibliometric analysis focusing on HRQOL in patients with. It underscores the need for more extensive and systematic research in this area, emphasizing the importance of a multidisciplinary approach. Despite advancements in medical treatments for IEI, there is a crucial need to focus on HRQOL to enhance patient satisfaction and overall well-being. The findings advocate for more personalized treatment plans and a better understanding of the psychosocial needs of patients with IEI to improve their quality of life.
Over the last decade, we have witnessed an explosion of information regarding the function of glycoconjugates, carbohydrate-binding proteins, and the elucidation of the sugar code. This progress has yielded not only important insights into fundamental areas of glycobiology but has also influenced other fields such as immunology and molecular medicine. A family of galactoside-binding proteins, called galectins, has emerged recently as a novel kind of bioactive molecules with powerful, immunoregulatory functions. Different members of this family have been shown to modulate positively or negatively multiple steps of the inflammatory response, such as cell-matrix interactions, cell trafficking, cell survival, cell-growth regulation, chemotaxis, and proinflammatory cytokine secretion. To introduce a comprehensive overview of these new advances, here we will explore the molecular mechanisms and biochemical pathways involved in these functions. We will also examine the role of these proteins in the modulation of different pathological processes, such as chronic inflammation, autoimmunity, infection, allergic reactions, and tumor spreading. Understanding the intimate mechanisms involved in galectin functions will help to delineate selective and novel strategies for disease intervention and diagnosis.
Pregnancy requires immune tolerance to the semiallogeneic fetus, mediated by regulatory T-cells and antiinflammatory cytokines (eg, interleukin 10 and transforming growth factor β), alongside a hypercoagulable state with elevated procoagulant factors and suppressed anticoagulants. In preeclampsia, a major cause of maternal and perinatal morbidity affecting 5% to 8% of pregnancies, excessive T-helper 1/ T-helper 17 responses, reduced Treg activity, and heightened platelet activation drive systemic inflammation, endothelial dysfunction, and microvascular thrombosis are established. Platelets, beyond hemostasis, modulate immune responses by interacting with neutrophils, monocytes, and T-cells via mediators such as P-selectin and CD40 ligand, promoting platelet-leukocyte aggregates, neutrophil extracellular traps, and proinflammatory cytokines (eg, interleukin 6 and tumor necrosis factor α). These interactions amplify coagulation via tissue factor expression, creating a pathogenic immune-hemostatic feedback loop. Deficiencies in coagulation regulators such as thrombomodulin and endothelial protein C receptor, exacerbate platelet activation and embryonic lethality, while galectins (eg, galectin 1 and 3) may mediate platelet-immune crosstalk. This article highlights the need for interdisciplinary research to elucidate these mechanisms, offering potential for novel biomarkers and therapeutic targets to improve management of vascular complications in pregnancy and maternal-fetal outcomes.
This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.
γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αβ T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells.
As an emerging sequencing technology, single-cell RNA sequencing (scRNA-Seq) has become a powerful tool for describing cell subpopulation classification and cell heterogeneity by achieving high-throughput and multidimensional analysis of individual cells and circumventing the shortcomings of traditional sequencing for detecting the average transcript level of cell populations. It has been applied to life science and medicine research fields such as tracking dynamic cell differentiation, revealing sensitive effector cells, and key molecular events of diseases. This review focuses on the recent technological innovations in scRNA-Seq, highlighting the latest research results with scRNA-Seq as the core technology in frontier research areas such as embryology, histology, oncology, and immunology. In addition, this review outlines the prospects for its innovative application in traditional Chinese medicine (TCM) research and discusses the key issues currently being addressed by scRNA-Seq and its great potential for exploring disease diagnostic targets and uncovering drug therapeutic targets in combination with multiomics technologies.
BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
Introduction: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease. Recently, growing evidence demonstrates that gut microbiota (GM) plays an important role in RA. But so far, no bibliometric studies pertaining to GM in RA have ever been published. This study attempts to depict the knowledge framework in this field from a holistic and systematic perspective based on the bibliometric analysis. Methods: Literature related to the involvement of GM in RA was searched and picked from the Web of Science Core Collection (WOSCC) database. The annual output, cooperation, hotspots, research status and development trend of this field were analyzed by bibliometric software (VOSviewer and Bibliometricx). Results: 255 original research articles and 204 reviews were included in the analysis. The articles in this field that can be retrieved in WOSCC were first published in 2004 and increased year by year since then. 2013 is a growth explosion point. China and the United States are the countries with the most contributions, and Harvard University is the affiliation with the most output. Frontiers in Immunology (total citations = 603) is the journal with the most publications and the fastest growth rate. eLife is the journal with the most citations (total citations = 1248). Scher, Jose U. and Taneja, Veena are the most productive and cited authors. The research in this field is mainly distributed in the evidence, mechanism and practical application of GM participating in RA through the analysis of keywords and documents. There is sufficient evidence to prove the close relationship between GM and RA, which lays the foundation for this field. This extended two colorful and tender branches of mechanism research and application exploration, which have made some achievements but still have broad exploration space. Recently, the keywords "metabolites", "metabolomics", "acid", "b cells", "balance", "treg cells", "probiotic supplementation" appeared most frequently, which tells us that research on the mechanism of GM participating in RA and exploration of its application are the hotspots in recent years. Discussion: Taken together, these results provide a data-based and objective introduction to the GM participating in RA, giving readers a valuable reference to help guide future research.
Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.
Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators. In addition, lactate inhibits the differentiation of monocytes and dendritic cells and also induces the inactivation of the cytotoxic T-lymphocytes. Through an analysis of recent studies, we conclude that lactate is a vital component of several ways of modulating the immune response at the stromal prostatic adenocarcinoma including TAM activation and cytotoxic T lymphocytes immunosuppression. Our review focuses on the impact of lactate on prostatic adenocarcinoma progression in terms of its immunology, and how this influences the therapy of this condition and the clinical outcome.
ResumenFactores pronsticos de mortalidad intrahospitalaria en pacientes ancianos con infeccin por COVID 19 ingresados a un hospital de tercer nivel en Bogot, ColombiaEl presente estudio tiene como objetivo establecer los factores pronsticos asociados al desarrollo de muerte intrahospitalaria en pacientes adultos mayores de 65 aos con infeccin por SARS-CoV2/COVID -19 confirmado en el Hospital Universitario Nacional de Colombia.Mtodos: Este es un estudio observacional analtico.Se evaluaron pacientes adultos mayores de 65 aos con diagnstico de infeccin por SARS-CoV2/COVID-19 confirmado.Los pacientes fueron estratificados por estado de fragilidad y funcionalidad.La mortalidad se determin a los 28 das y se cre un modelo de regresin logstica incondicional, ajustando por factores de confusin.La significancia estadstica se estableci en p 0,05.Resultados: 170 pacientes fueron estratificados en sobrevivientes y no sobrevivientes .El porcentaje de hombres en los sobrevivientes y no sobrevivientes fue similar, sin diferencias significativas en la edad promedio entre ambos grupos, tampoco en relacin a la presencia de sntomas.En el anlisis multivariado, las siguientes variables predijeron la ocurrencia del desenlace mortalidad a 28 das: fragilidad, antecedente de cncer, SDRA, lesin renal aguda y SOFA.Conclusiones: La tasa mortalidad a 28 das en pacientes adultos mayores de 65 aos con infeccin por COVID 19 en este estudio fue de 38%.Al ajustar por antecedente de cncer, desarrollo de lesin renal aguda, SDRA, puntuacin SOFA y PAFI al ingreso, la fragilidad se asoci con una mayor mortalidad en la poblacin estudiada.
Adaptive natural killer (NK) cell memory represents a new frontier in immunology. Work over the last decade has discovered and confirmed the existence of NK cells with antigen-specific memories, which had previously been considered a unique property of T and B cells. These findings have shown that antigen-specific NK cells gain their specificity without the use of RAG proteins, representing a novel mechanism for generating antigen specificity, but the details of this mechanism have remained a mystery. We have discovered that members of the Ly49 family of surface receptors are critically involved in both the sensitization and the challenge phases of an NK cell memory response, as is antigen presentation from their binding partner, the class I MHC. Moreover, we demonstrate that the Ly49-interacting component of a presented antigen dictates the specificity of the NK cell memory response, implicating Ly49 receptors themselves in antigen-specific recognition. Finally, we demonstrate that adaptive NK cell memories can protect against an otherwise lethal melanoma without T cell or B cell support. These findings offer insight into the mechanism behind NK cell antigen specificity and demonstrate the clinical potential of this adaptive immune cell.
sensor, participating in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, S100A8/A9 is released actively and exerts a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate biomarker for diagnosis and follow-up as well as a predictive indicator of therapeutic responses to inflammation-associated diseases. As blockade of S100A8/A9 activity using small-molecule inhibitors or antibodies improves pathological conditions in murine models, the heterodimer has potential as a therapeutic target. In this review, we provide a comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 and highlight its application as a diagnostic and therapeutic target in inflammation-associated diseases.