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Frontiers in Immunology 2020The contribution of dendritic cell (DC) antigen cross-presentation to the activation of CD8 T lymphocytes for immune defense against tumors, viruses, and intracellular... (Review)
Review
The contribution of dendritic cell (DC) antigen cross-presentation to the activation of CD8 T lymphocytes for immune defense against tumors, viruses, and intracellular pathogens has been recognized widely. Although originally thought to be an exclusive characteristic of DCs, recently also other immune cells, particularly macrophages, have been shown capable of cross-presentation. Here we provide an overview of and evidence on cross-presentation by macrophages. As we discuss, it is now firmly established that various types of tissue-resident macrophages are able to cross-present via similar cellular pathways as DCs. This is based on a wide range of antigens in macrophages from many different tissue origins such as blood, tumors, and lymphoid tissue. However, the physiological relevance of macrophage cross-presentation with potential contributions to activation of CD8 T lymphocytes is still mostly unknown. While cross-presentation by various types of proinflammatory macrophages might be involved in cross-priming of naive CD8 T lymphocytes, it might also be involved in local reactivation of memory and/or effector CD8 T lymphocytes. Moreover, cross-presentation by anti-inflammatory macrophages could be related to immune tolerance. Because cross-presentation promotes the initiation and potentiation of antigen-specific CD8 T lymphocyte responses, stimulating macrophages to cross-present antigen might be a promising strategy for antitumor or antiviral therapies.
Topics: Animals; Antigen Presentation; Antigens; Biomarkers; CD8-Positive T-Lymphocytes; Cell Communication; Cross-Priming; Dendritic Cells; Humans; Lymphocyte Activation; Lymphoid Tissue; Macrophages; Organ Specificity; Signal Transduction
PubMed: 32733446
DOI: 10.3389/fimmu.2020.01276 -
Nutrients Aug 2019A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune...
A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune system must be able to distinguish self from non-self and furthermore discriminate between non-self molecules which are harmful (e.g., those from pathogens) and innocuous non-self molecules (e.g., from food). This Special Issue of Nutrients explores the relationship between diet and nutrients and immune function. In this preface, we outline the key functions of the immune system, and how it interacts with nutrients across the life course, highlighting the work included within this Special Issue. This includes the role of macronutrients, micronutrients, and the gut microbiome in mediating immunological effects. Nutritional modulation of the immune system has applications within the clinical setting, but can also have a role in healthy populations, acting to reduce or delay the onset of immune-mediated chronic diseases. Ongoing research in this field will ultimately lead to a better understanding of the role of diet and nutrients in immune function and will facilitate the use of bespoke nutrition to improve human health.
Topics: Diet; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Immune System; Inflammation; Lymphoid Tissue; Nutritional Status
PubMed: 31426423
DOI: 10.3390/nu11081933 -
Frontiers in Immunology 2022CXCL13 is a B-cell chemokine produced mainly by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells. By binding... (Review)
Review
CXCL13 is a B-cell chemokine produced mainly by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells. By binding to its receptor, CXCR5, CXCL13 plays an important role in lymphoid neogenesis, lymphoid organization, and immune responses. Recent studies have found that CXCL13 and its receptor CXCR5 are implicated in the pathogenesis of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, primary Sjögren's syndrome, myasthenia gravis, and inflammatory bowel disease. In this review, we discuss the biological features of CXCL13 and CXCR5 and the recent findings on the pathogenic roles of the CXCL13/CXCR5 axis in autoimmune diseases. Furthermore, we discuss the potential role of CXCL13 as a disease biomarker and therapeutic target in autoimmune diseases.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Chemokine CXCL13; Dendritic Cells, Follicular; Humans; Lymphoid Tissue; Receptors, CXCR5
PubMed: 35309354
DOI: 10.3389/fimmu.2022.850998 -
BMJ Paediatrics Open Apr 2023Adenoids (nasopharyngeal tonsils), being part of Waldeyer's ring, are masses of lymphoid tissues located at the junction of the roof and the posterior wall of the... (Review)
Review
Adenoids (nasopharyngeal tonsils), being part of Waldeyer's ring, are masses of lymphoid tissues located at the junction of the roof and the posterior wall of the nasopharynx. Adenoids play an important role in the development of the immune system and serve as a defence against infections, being the first organs that come into contact with respiratory and digestive antigens. The causes of adenoid hypertrophy are not fully known. They are most likely associated with aberrant immune reactions, infections, environmental exposures and hormonal or genetic factors. The aim of this review is to summarise the current knowledge of adenoid hypertrophy in children and associated diseases. Adenoid hypertrophy has many clinical manifestations that are frequent in the paediatric population and is accompanied by various comorbidities.
Topics: Humans; Child; Adenoids; Clinical Relevance; Nasopharynx; Lymphoid Tissue; Hypertrophy
PubMed: 37045541
DOI: 10.1136/bmjpo-2022-001710 -
American Journal of Physiology. Renal... Dec 2018Acute kidney injury (AKI) is a common clinical state resulting from pathogenic conditions such as ischemic and toxic insults. The pathophysiology of AKI shares common... (Review)
Review
Acute kidney injury (AKI) is a common clinical state resulting from pathogenic conditions such as ischemic and toxic insults. The pathophysiology of AKI shares common pathogenic denominators including cell death/injury, inflammation, and fibrosis, regardless of the initiating insults. Recent clinical studies have shown that a single episode of AKI can lead to subsequent chronic kidney disease (CKD). Although the involvement of multiple types of cells in the pathophysiology of AKI is becoming increasingly clear, the precise mechanisms for this "AKI to CKD progression" are still unknown, and no drug has been shown to halt this progression. An increasing number of epidemiological studies have also revealed that the presence of aging greatly increases the risk of AKI to CKD progression, and chronic inflammation is increasingly recognized as an important determinant factor for this progression. In this review article, we first describe the current understanding of the pathophysiology of AKI to CKD progression based on multiple types of cells. In particular, we will highlight the recent findings in regard to the mechanisms for chronic inflammation after AKI. Subsequently, we will focus on the mechanisms responsible for the increased risk of AKI to CKD progression in the elderly. Finally, we highlight our recent finding of age-dependent tertiary lymphoid tissue formation and its roles in AKI to CKD progression and speculate on the potential therapeutic opportunities that come from targeting aberrant inflammation after AKI.
Topics: Acute Kidney Injury; Age Factors; Aging; Animals; Disease Progression; Humans; Immunosenescence; Inflammation; Inflammation Mediators; Kidney; Lymphoid Tissue; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Signal Transduction
PubMed: 30156114
DOI: 10.1152/ajprenal.00195.2018 -
Immunity May 2018Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains...
Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19 T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19 TRCs, likely including cholesterol-25-hydroxylase cells located at the T-zone perimeter, Cxcl9 TRCs in the T-zone and interfollicular region, CD34 SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase SCs in the medullary cords, and Nr4a1 SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and provide evidence that many SCs are in an activated state.
Topics: Animals; Chemokine CCL19; Dendritic Cells, Follicular; Female; Lymph Nodes; Lymphoid Tissue; Mice, Inbred C57BL; Sequence Analysis, RNA; Single-Cell Analysis; Stromal Cells; Transcriptome
PubMed: 29752062
DOI: 10.1016/j.immuni.2018.04.006 -
Toxicologic Pathology Aug 2019The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of...
The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced. Three terms are listed for each diagnosis. The rationale for this approach and guidance for its application to toxicologic pathology are described in detail below.
Topics: Animals; Animals, Laboratory; Biomedical Research; Bone Marrow; Bone Marrow Diseases; Lymphatic Diseases; Lymphoid Tissue; Mice; Rats; Terminology as Topic
PubMed: 31526133
DOI: 10.1177/0192623319867053 -
Immunity Feb 2019Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000...
Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4 regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation.
Topics: Adaptation, Physiological; Animals; Cell Line, Tumor; Cell Movement; Colon; Humans; Immunologic Memory; Lymphoid Tissue; Mice, Transgenic; Neoplasms, Experimental; Single-Cell Analysis; Skin; Spleen; T-Lymphocytes, Regulatory; Transcriptome
PubMed: 30737144
DOI: 10.1016/j.immuni.2019.01.001 -
Clinical and Experimental Rheumatology 2018The formation of lymphomononuclear cell infiltrates organising as periductal infiltrates in the salivary glands of patients with primary Sjögren's syndrome (pSS) is one... (Review)
Review
The formation of lymphomononuclear cell infiltrates organising as periductal infiltrates in the salivary glands of patients with primary Sjögren's syndrome (pSS) is one of the hallmarks of the disease. Historically, the clinical role of salivary gland histopathology, most commonly performed on labial salivary gland biopsies, has been confined to the clinical classification and diagnosis of pSS whereby according to the ACR-EULAR a positive histopathology finding is a requirement for the diagnosis of pSS in the absence of anti-Ro/SSA antibodies. In recent years, further understanding of the heterogeneity of the immune cell infiltration and organisation within the salivary glands of pSS patients and its correlation with clinical manifestations of the disease has led to propose salivary gland histopathology as a novel tool able to identify patients at higher risk of developing more severe extraglandular manifestations and lymphoma. Furthermore, recent clinical developments in ongoing randomised clinical trials with novel biologics in pSS have focused on salivary glands histopathology to inform on patients stratification based on target validation, proof of drug efficacy and mechanisms of response/resistance to therapy. However, lack of standardisation of methodology and analysis has hindered the reproducibility of data from different groups and no definitive evidence in support of the use of salivary glands histopathology to inform clinical management of patients with pSS has been provided. In this review, we summarise recent evidence highlighting the promises and pitfalls of salivary glands histopathology in pSS emphasising the need for an international consensus on standardisation of methodology with validation in large prospective multicentre initiatives.
Topics: Antirheumatic Agents; Biomarkers; Biopsy; Decision Support Techniques; Immunohistochemistry; Lymphoid Tissue; Predictive Value of Tests; Reproducibility of Results; Risk Assessment; Risk Factors; Salivary Glands; Severity of Illness Index; Sjogren's Syndrome; Treatment Outcome
PubMed: 30156550
DOI: No ID Found -
Immunity Jan 2018Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what...
Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.
Topics: Animals; Cell Movement; Colitis; Colon; Cytokines; Flow Cytometry; Fluorescent Antibody Technique; Ligands; Lymphocytes; Lymphoid Tissue; Mice; Oxysterols; Real-Time Polymerase Chain Reaction; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 29343433
DOI: 10.1016/j.immuni.2017.11.020