Genetic association analysis and frequency of NUDT15*3 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease in a large Dutch cohort
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Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles. Macrophages, as key immune cells, critically regulate inflammation through polarization into different phenotypes. In recent years, the role of macrophages in inflammation-related degenerative diseases, such as intervertebral disc degeneration, has been increasingly recognized. Macrophages construct the inflammatory microenvironment of the intervertebral disc and are involved in regulating intervertebral disc cell activities, extracellular matrix metabolism, intervertebral disc vascularization, and innervation, profoundly influencing the progression of disc degeneration. To gain a deeper understanding of the inflammatory microenvironment of intervertebral disc degeneration, this review will summarize the role of macrophages in the pathological process of intervertebral disc degeneration, analyze the regulatory mechanisms involving macrophages, and review therapeutic strategies targeting macrophage modulation for the treatment of intervertebral disc degeneration. These insights will be valuable for the treatment and research directions of intervertebral disc degeneration.
Anti-inflammatory Prowess of endothelial progenitor cells in the realm of biology and medicine
Endothelial inflammation plays a crucial role in vascular-related diseases, a leading cause of global mortality. Among various cellular players, endothelial progenitor cells (EPCs) emerge as non-differentiated endothelial cells circulating in the bloodstream. Recent evidence highlights the transformative role of EPCs in shifting from an inflammatory/immunosuppressive crisis to an anti-inflammatory/immunomodulatory response. Despite the importance of these functions, the regulatory mechanisms governing EPC activities and their physiological significance in vascular regenerative medicine remain elusive. Surprisingly, the current literature lacks a comprehensive review of EPCs’ effects on inflammatory processes. This narrative review aims to fill this gap by exploring the cutting-edge role of EPCs against inflammation, from molecular intricacies to broader medical perspectives. By examining how EPCs modulate inflammatory responses, we aim to unravel their anti-inflammatory significance in vascular regenerative medicine, deepening insights into EPCs’ molecular mechanisms and guiding future therapeutic strategies targeting vascular-related diseases.
Type 2 immunity in allergic diseases
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality
Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I–III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naïve mTNBC patients showed increased classical monocytes and neutrophils. Transcriptional, proteomic, and functional analyses revealed that neutrophils in mTNBC exhibited enhanced migratory capacity, elevated granule proteins, and higher ROS production. Some immune changes, such as reduced non-switched B cells and heightened neutrophil migration, were evident in earlier TNBC stages. This study comprehensively maps systemic immunity in TNBC, guiding future research on patient stratification and immunomodulation strategies.
Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis
Osteoarthritis (OA) poses a significant challenge in orthopedics. Inflammatory pathways are regarded as central mechanisms in the onset and progression of OA. Growing evidence suggests that senescence acts as a mediator in inflammation-induced OA. Given the lack of effective treatments for OA, there is an urgent need for a clearer understanding of its pathogenesis. In this review, we systematically summarize the cross-talk between cellular senescence and inflammation in OA. We begin by focusing on the mechanisms and hallmarks of cellular senescence, summarizing evidence that supports the relationship between cellular senescence and inflammation. We then discuss the mechanisms of interaction between cellular senescence and inflammation, including senescence-associated secretory phenotypes (SASP) and the effects of pro- and anti-inflammatory interventions on cellular senescence. Additionally, we focus on various types of cellular senescence in OA, including senescence in cartilage, subchondral bone, synovium, infrapatellar fat pad, stem cells, and immune cells, elucidating their mechanisms and impacts on OA. Finally, we highlight the potential of therapies targeting senescent cells in OA as a strategy for promoting cartilage regeneration.
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