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Pain Apr 2024The past 20 years have seen a dramatic shift in our understanding of the role of the immune system in initiating and maintaining pain. Myeloid cells, including... (Review)
Review
The past 20 years have seen a dramatic shift in our understanding of the role of the immune system in initiating and maintaining pain. Myeloid cells, including macrophages, dendritic cells, Langerhans cells, and mast cells, are increasingly implicated in bidirectional interactions with nerve fibres in rodent pain models. However, our understanding of the human setting is still poor. High-dimensional functional analyses have substantially changed myeloid cell classifications, with recently described subsets such as epidermal dendritic cells and DC3s unveiling new insight into how myeloid cells interact with nerve fibres. However, it is unclear whether this new understanding has informed the study of human chronic pain. In this article, we perform a scoping review investigating neuroimmune interactions between myeloid cells and peripheral nerve fibres in human chronic pain conditions. We found 37 papers from multiple pain states addressing this aim in skin, cornea, peripheral nerve, endometrium, and tumour, with macrophages, Langerhans cells, and mast cells the most investigated. The directionality of results between studies was inconsistent, although the clearest pattern was an increase in macrophage frequency across conditions, phases, and tissues. Myeloid cell definitions were often outdated and lacked correspondence with the stated cell types of interest; overreliance on morphology and traditional structural markers gave limited insight into the functional characteristics of investigated cells. We therefore critically reappraise the existing literature considering contemporary myeloid cell biology and advocate for the application of established and emerging high-dimensional proteomic and transcriptomic single-cell technologies to clarify the role of specific neuroimmune interactions in chronic pain.
Topics: Female; Humans; Chronic Pain; Proteomics; Macrophages; Myeloid Cells; Cell Communication
PubMed: 37975868
DOI: 10.1097/j.pain.0000000000003106 -
Microbiology Spectrum Nov 2016Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis, and other effector functions. There are several types of... (Review)
Review
Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis, and other effector functions. There are several types of complement receptors on myeloid cells, including G protein-coupled receptors for localizing the source of complement activation, and three sets of type I transmembrane proteins that link complement to phagocytosis: complement receptor 1, having an extracellular domain with tandem complement regulatory repeats; complement receptors 3 and 4, which are integrin family receptors comprising heterodimers of type I transmembrane subunits; and VSIG4, a member of the Ig superfamily. This review will focus on the role of the different classes of complement receptors and how their activities are integrated in the setting of immune tolerance and inflammatory responses.
Topics: Animals; Cell Adhesion; Humans; Myeloid Cells; Phagocytosis; Receptors, Complement
PubMed: 27809953
DOI: 10.1128/microbiolspec.MCHD-0034-2016 -
International Immunopharmacology Jun 2024Tumor microenvironment (TME), is characterized by a complex and heterogenous composition involving a substantial population of immune cells. Myeloid cells comprising... (Review)
Review
Tumor microenvironment (TME), is characterized by a complex and heterogenous composition involving a substantial population of immune cells. Myeloid cells comprising over half of the solid tumor mass, are undoubtedly one of the most prominent cell populations associated with tumors. Studies have unambiguously established that myeloid cells play a key role in tumor development, including immune suppression, pro-inflammation, promote tumor metastasis and angiogenesis, for example, tumor-associated macrophages promote tumor progression in a variety of common tumors, including lung cancer, through direct or indirect interactions with the TME. However, due to previous technological constraints, research on myeloid cells often tended to be conducted as studies with low throughput and limited resolution. For example, the conventional categorization of macrophages into M1-like and M2-like subsets based solely on their anti-tumor and pro-tumor roles has disregarded their continuum of states, resulting in an inadequate analysis of the high heterogeneity characterizing myeloid cells. The widespread adoption of single-cell RNA sequencing (scRNA-seq) in tumor immunology has propelled researchers into a new realm of understanding, leading to the establishment of novel subsets and targets. In this review, the origin of myeloid cells in high-incidence cancers, the functions of myeloid cell subsets examined through traditional and single-cell perspectives, as well as specific targeting strategies, are comprehensively outlined. As a result of this endeavor, we will gain a better understanding of myeloid cell heterogeneity, as well as contribute to the development of new therapeutic approaches.
Topics: Humans; Tumor Microenvironment; Neoplasms; Myeloid Cells; Animals; Single-Cell Analysis
PubMed: 38735257
DOI: 10.1016/j.intimp.2024.112253 -
Frontiers in Immunology 2023Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established,...
Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established, the underlying mechanisms remain to be investigated further. Here we studied a novel protein prokineticin 2 (Prok2, also known as Bv8) as a key pro-tumoral factor in CRC progression in and settings. Human colorectal tumor tissues, myeloid cell lines (U937 cells and HL60 cells) and colorectal cancer cell line (Caco-2 cells) were used for various studies. Myeloid cell infiltration (especially neutrophils) and Bv8 accumulation were detected in human colorectal tumor tissue with immunostaining. The chemotactic effects of Bv8 on myeloid cells were presented in the transwell assay and chemotaxis assy. Cultured CRC cells treated with myeloid cells or Bv8 produced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF). Furthermore, ROS and VEGF acted as pro-angiogenesis buffer in myeloid cell-infiltrated CRC microenvironment. Moreover, myeloid cells or Bv8 enhanced energy consumption of glycolysis ATP and mitochondria ATP of CRC cells. Interestingly, myeloid cells increased CRC cell viability, but CRC cells decreased the viability of myeloid cells. ERK signalling pathway in CRC cells was activated in the presence of Bv8 or co-cultured myeloid cells. In conclusion, our data indicated the vital roles of Bv8 in myeloid cell infiltration and CRC development, suggesting that Bv8 may be a potential therapeutic target for colorectal cancer-related immunotherapy.
Topics: Humans; Vascular Endothelial Growth Factor A; Caco-2 Cells; Reactive Oxygen Species; Neuropeptides; Myeloid Cells; Cell Movement; Colorectal Neoplasms; Vascular Endothelial Growth Factors; Adenosine Triphosphate; Tumor Microenvironment
PubMed: 37090721
DOI: 10.3389/fimmu.2023.1158045 -
EMBO Reports May 2019Inflamed and infected tissue sites are characterised by oxygen and nutrient deprivation. The cellular adaptations to insufficient oxygenation, hypoxia, are mainly... (Review)
Review
Inflamed and infected tissue sites are characterised by oxygen and nutrient deprivation. The cellular adaptations to insufficient oxygenation, hypoxia, are mainly regulated by a family of transcription factors known as hypoxia-inducible factors (HIFs). The protein members of the HIF signalling pathway are critical regulators of both the innate and adaptive immune responses, and there is an increasing body of evidence to suggest that the elicited changes occur through cellular metabolic reprogramming. Here, we review the literature on innate immunometabolism to dateĀ and discuss the role of hypoxia in innate cell metabolic reprogramming, and how this determines immune responses.
Topics: Adaptive Immunity; Animals; Cell Hypoxia; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunity, Innate; Inflammation; Myeloid Cells; Oxygen; Signal Transduction
PubMed: 30872317
DOI: 10.15252/embr.201847388 -
Cancer Metastasis Reviews Mar 2011Tumour development is accompanied by an enhanced haematopoiesis. This is not a widespread activation since only cells belonging to the myelo-monocytic compartment are... (Review)
Review
Tumour development is accompanied by an enhanced haematopoiesis. This is not a widespread activation since only cells belonging to the myelo-monocytic compartment are expanded and mobilized from primary sites of haematopoiesis to other organs, reaching also the tumour stroma. This process occurs early during tumour formation but becomes more evident in advanced disease. Far from being a simple, unwanted consequence of cancer development, accumulation of myelo-monocytitc cells plays a role in tumour vascularization, local spreading, establishment of metastasis at distant sites, and contribute to create an environment unfavourable for the adoptive immunity against tumour-associated antigens. Myeloid populations involved in these process are likely different but many cells, expanded in primary and secondary lymphoid organs of tumour-bearing mice, share various levels of the CD11b and Gr-1 (Ly6C/G) markers. CD11b(+)Gr-1(+) cells are currently named myeloid-derived suppressor cells for their ability to inhibit T lymphocyte responses in tumour-bearing hosts. In this manuscript, we review the recent literature on tumour-conditioned myeloid subsets that assist tumour growth, both in mice and humans.
Topics: Animals; Humans; Myeloid Cells; Neoplasms
PubMed: 21267772
DOI: 10.1007/s10555-011-9268-1 -
Cold Spring Harbor Perspectives in... May 2020Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor... (Review)
Review
Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor cells from their constraining basement membrane at the primary site, migration and intravasation into the circulation, survival in the circulation, extravasation into the secondary organ, and survival and growth at the secondary site. During these steps, tumor and immune cells interact and influence each other both within the tumor microenvironment and systemically. In particular, myeloid cells such as monocytes, macrophages, neutrophils, and myeloid-derived suppressor cells (myeloid regulatory cells) have been shown to play important roles in the metastatic process. These interactions open new avenues for targeting cancer metastasis, especially given the increasing interest in development of cancer immunotherapies. In this review, we describe the currently reported pathways and mechanisms involved in myeloid cell enhancement of the metastatic cascade.
Topics: Animals; Humans; Immunotherapy; Myeloid Cells; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 31548218
DOI: 10.1101/cshperspect.a038026 -
Signal Transduction and Targeted Therapy Oct 2021Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is... (Review)
Review
Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is an important driving factor that leads to severe COVID-19 cases and subsequent death. This review briefly summarizes the results of single-cell sequencing of peripheral blood, lung tissue, and cerebrospinal fluid of COVID-19 patients and describes the differentiation trajectory of myeloid cells in patients. Moreover, we describe the function and mechanism of abnormal differentiation of myeloid cells to promote disease progression. Targeting myeloid cell-derived cytokines or checkpoints is essential in developing a combined therapeutic strategy for patients with severe COVID-19.
Topics: Animals; COVID-19; Cell Differentiation; Cellular Microenvironment; Humans; Myeloid Cells; SARS-CoV-2; Single-Cell Analysis
PubMed: 34707085
DOI: 10.1038/s41392-021-00792-0 -
Current Molecular Medicine 2021Myeloid cell leukemia 1 (Mcl-1) is a member of the Bcl-2 family of proteins with anti-apoptotic activity. It plays a key role in the regulation of the intrinsic pathway... (Review)
Review
Myeloid cell leukemia 1 (Mcl-1) is a member of the Bcl-2 family of proteins with anti-apoptotic activity. It plays a key role in the regulation of the intrinsic pathway of apoptosis. Moreover, Mcl-1 is correlated with the progression and drug-resistance of various cancers. The development of inhibitors of Mcl-1 may provide effective cancer therapies. While the inhibitors of other Bcl-2 anti-apoptotic proteins have been well explored, the discovery of Mcl-1inhibitors with high selectivity has been challenging. In this review, we summarize the recent literature on small molecule and peptide inhibitors of Mcl-1, which are divided into different types including peptide inhibitors, gossypol derivatives, marinopyrrole derivatives, S1 derivatives, indole derivatives, quinoline derivatives, S63845, AZD5991, AMG176, etc. Their biological activities are also summarized. Mcl-1 is a valid drug target and inhibition of Mcl-1 with a small molecule inhibitor is a promising strategy for cancer therapy.
Topics: Antineoplastic Agents; Apoptosis; Humans; Leukemia; Myeloid Cells; Peptides; Small Molecule Libraries
PubMed: 32990536
DOI: 10.2174/1566524020666200929121016 -
Annals of the New York Academy of... Sep 2021On May 2017, the World Health Organization recognized sepsis as a global health priority. Sepsis profoundly perturbs immune homeostasis by initiating a complex response... (Review)
Review
On May 2017, the World Health Organization recognized sepsis as a global health priority. Sepsis profoundly perturbs immune homeostasis by initiating a complex response that varies over time, with the concomitant occurrence of pro- and anti-inflammatory mechanisms. Sepsis deeply impacts myeloid cell response. Different mechanisms are at play, such as apoptosis, endotoxin tolerance, metabolic failure, epigenetic reprogramming, and central regulation. This induces systemic effects on circulating immune cells and impacts progenitors locally in lymphoid organs. In the bone marrow, a progressive shift toward the release of immature myeloid cells (including myeloid-derived suppressor cells), at the expense of mature neutrophils, takes place. Circulating dendritic cell number remains dramatically low and monocytes/macrophages display an anti-inflammatory phenotype and reduced antigen presentation capacity. Intensity and persistence of these alterations are associated with increased risk of deleterious outcomes in patients. Thus, myeloid cells dysfunctions play a prominent role in the occurrence of sepsis-acquired immunodeficiency. For the most immunosuppressed patients, this paves the way for clinical trials evaluating immunoadjuvant molecules (granulocyte-macrophage colony-stimulating factor and interferon gamma) aimed at restoring homeostatic myeloid cell response. Our review offers a summary of sepsis-induced myeloid cell dysfunctions and current therapeutic strategies proposed to target these defects in patients.
Topics: Animals; Biomarkers; Disease Susceptibility; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Myeloid Cells; Myeloid-Derived Suppressor Cells; Organ Specificity; Sepsis
PubMed: 32202669
DOI: 10.1111/nyas.14333