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Atherosclerosis serves as the primary catalyst for numerous cardiovascular diseases. Growing evidence suggests that the immune response is involved in every stage of atherosclerotic plaque evolution. Rapid, but not specific, innate immune arms, including neutrophils, monocytes/macrophages, dendritic cells (DCs) and other innate immune cells, as well as pattern-recognition receptors and various inflammatory mediators, contribute to atherogenesis. The specific adaptive immune response, governed by T cells and B cells, antibodies, and immunomodulatory cytokines potently regulates disease activity and progression. In the inflammatory microenvironment, the heterogeneity of leukocyte subpopulations plays a very important regulatory role in plaque evolution. With advances in experimental techniques, the fine mechanisms of immune system involvement in atherosclerotic plaque evolution are becoming known. In this review, we examine the critical immune responses involved in atherosclerotic plaque evolution, in particular, looking at atherosclerosis from the perspective of evolutionary immunobiology. A comprehensive understanding of the interplay between plaque evolution and plaque immunity provides clues for strategically combating atherosclerosis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to- GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and antiinflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulat ion of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body's anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Lactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation. Methods: RAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations. Results: The in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis. Conclusions: Lactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotes the repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation. [ABSTRACT FROM AUTHOR]

Atherosclerosis serves as the primary catalyst for numerous cardiovascular diseases. Growing evidence suggests that the immune response is involved in every stage of atherosclerotic plaque evolution. Rapid, but not specific, innate immune arms, including neutrophils, monocytes/macrophages, dendritic cells (DCs) and other innate immune cells, as well as pattern-recognition receptors and various inflammatory mediators, contribute to atherogenesis. The specific adaptive immune response, governed by T cells and B cells, antibodies, and immunomodulatory cytokines potently regulates disease activity and progression. In the inflammatory microenvironment, the heterogeneity of leukocyte subpopulations plays a very important regulatory role in plaque evolution. With advances in experimental techniques, the fine mechanisms of immune system involvement in atherosclerotic plaque evolution are becoming known. In this review, we examine the critical immune responses involved in atherosclerotic plaque evolution, in particular, looking at atherosclerosis from the perspective of evolutionary immunobiology. A comprehensive understanding of the interplay between plaque evolution and plaque immunity provides clues for strategically combating atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pi, Wang, Wang, Zhang, He, Zheng, Yin, Zhao and Jiang.)

Wound healing is a dynamic and highly regulated process that can be separated into three overlapping and interdependent phases: inflammation, proliferation, and remodelling. This review focuses on the inflammation stage, as it is the key stage of wound healing and plays a vital role in the local immune response and determines the progression of wound healing. Inflammatory cells, the main effector cells of the inflammatory response, have been widely studied, but little attention has been paid to the immunomodulatory effects of wound healing in non-inflammatory cells and the extracellular matrix. In this review, we attempt to deepen our understanding of the wound-healing microenvironment in the inflammatory stage by focusing on the interactions between cells and the extracellular matrix, as well as their role in regulating the immune response during the inflammatory stage. We hope our findings will provide new ideas for promoting tissue regeneration through immune regulation. [ABSTRACT FROM AUTHOR]

Wound healing is a dynamic and highly regulated process that can be separated into three overlapping and interdependent phases: inflammation, proliferation, and remodelling. This review focuses on the inflammation stage, as it is the key stage of wound healing and plays a vital role in the local immune response and determines the progression of wound healing. Inflammatory cells, the main effector cells of the inflammatory response, have been widely studied, but little attention has been paid to the immunomodulatory effects of wound healing in non-inflammatory cells and the extracellular matrix. In this review, we attempt to deepen our understanding of the wound-healing microenvironment in the inflammatory stage by focusing on the interactions between cells and the extracellular matrix, as well as their role in regulating the immune response during the inflammatory stage. We hope our findings will provide new ideas for promoting tissue regeneration through immune regulation.

Periodontitis is a highly prevalent chronic inflammatory disease leading to periodontal tissue breakdown and subsequent tooth loss, in which excessive host immune response accounts for most of the tissue damage and disease progression. Despite of the imperative need to develop host modulation therapy, the inflammatory responses and cell population dynamics which are finely tuned by the pathological microenvironment in periodontitis remained unclear. To investigate the local microenvironment of the inflammatory response in periodontitis, 10 periodontitis patients and 10 healthy volunteers were involved in this study. Single-cell transcriptomic profilings of gingival tissues from two patients and two healthy donors were performed. Histology, immunohistochemistry, and flow cytometry analysis were performed to further validate the identified cell subtypes and their involvement in periodontitis. Based on our single-cell resolution analysis, we identified HLA-DR-expressing endothelial cells and CXCL13+ fibroblasts which are highly associated with immune regulation. We also revealed the involvement of the proinflammatory NLRP3+ macrophages in periodontitis. We further showed the increased cell-cell communication between macrophage and T/B cells in the inflammatory periodontal tissues. Our data generated an intriguing catalog of cell types and interaction networks in the human gingiva and identified new inflammation-promoting cell subtypes involved in chronic periodontitis, which will be helpful in advancing host modulation therapy. [ABSTRACT FROM AUTHOR]

Periodontitis is a highly prevalent chronic inflammatory disease leading to periodontal tissue breakdown and subsequent tooth loss, in which excessive host immune response accounts for most of the tissue damage and disease progression. Despite of the imperative need to develop host modulation therapy, the inflammatory responses and cell population dynamics which are finely tuned by the pathological microenvironment in periodontitis remained unclear. To investigate the local microenvironment of the inflammatory response in periodontitis, 10 periodontitis patients and 10 healthy volunteers were involved in this study. Single-cell transcriptomic profilings of gingival tissues from two patients and two healthy donors were performed. Histology, immunohistochemistry, and flow cytometry analysis were performed to further validate the identified cell subtypes and their involvement in periodontitis. Based on our single-cell resolution analysis, we identified HLA-DR-expressing endothelial cells and CXCL13+ fibroblasts which are highly associated with immune regulation. We also revealed the involvement of the proinflammatory NLRP3+ macrophages in periodontitis. We further showed the increased cell-cell communication between macrophage and T/B cells in the inflammatory periodontal tissues. Our data generated an intriguing catalog of cell types and interaction networks in the human gingiva and identified new inflammation-promoting cell subtypes involved in chronic periodontitis, which will be helpful in advancing host modulation therapy.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori ( H. pylori ) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Zhang, Shen, Liu, Zhu, Fang, Pan and Liu.)

Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulation of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body's anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zhou, Cao, Chen, Gong, Zhang, Qiang, Lu and Cao.)

Background: Lactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation., Methods: RAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations., Results: The in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis., Conclusions: Lactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Yu, Yan, Liang, Ma, Long, Du, Mao and Liu.)