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Frontiers in Immunology 2021Interactions between the lung epithelium and the immune system involve a tight regulation to prevent inappropriate reactions and have been connected to several pulmonary... (Review)
Review
Interactions between the lung epithelium and the immune system involve a tight regulation to prevent inappropriate reactions and have been connected to several pulmonary diseases. Although the distal lung epithelium and local immunity have been implicated in the pathogenesis and disease course of idiopathic pulmonary fibrosis (IPF), consequences of their abnormal interplay remain less well known. Recent data suggests a two-way process, as illustrated by the influence of epithelial-derived periplakin on the immune landscape or the effect of macrophage-derived IL-17B on epithelial cells. Additionally, damage associated molecular patterns (DAMPs), released by damaged or dying (epithelial) cells, are augmented in IPF. Next to "sterile inflammation", pathogen-associated molecular patterns (PAMPs) are increased in IPF and have been linked with lung fibrosis, while outer membrane vesicles from bacteria are able to influence epithelial-macrophage crosstalk. Finally, the advent of high-throughput technologies such as microbiome-sequencing has allowed for the identification of a disease-specific microbial environment. In this review, we propose to discuss how the interplays between the altered distal airway and alveolar epithelium, the lung microbiome and immune cells may shape a pro-fibrotic environment. More specifically, it will highlight DAMPs-PAMPs pathways and the specificities of the IPF lung microbiome while discussing recent elements suggesting abnormal mucosal immunity in pulmonary fibrosis.
Topics: Alarmins; Bacteria; Epithelial Cells; Humans; Idiopathic Pulmonary Fibrosis; Inflammation; Lung; Microbiota; Pathogen-Associated Molecular Pattern Molecules; Respiratory Mucosa
PubMed: 34093523
DOI: 10.3389/fimmu.2021.631235 -
European Journal of Trauma and... Jun 2018This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often... (Review)
Review
This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often pleiotropic effects of a DAMP, it is difficult to describe its "friend or foe" role in post-traumatic inflammation and regeneration, both systemically as well locally in tissues. DAMP can be used as biomarkers to indicate or monitor disease or injury severity, but also may serve as clinically applicable parameters for better indication and timing of surgery. Due to the inflammatory processes at the local tissue level or the systemic level, the precise role of DAMP is not always clear to define. While in vitro and experimental studies allow for the detection of these biomarkers at the different levels of an organism-cellular, tissue, circulation-this is not always easily transferable to the human setting. Increased knowledge exploring the dual role of DAMP after trauma, and concentrating on their nuclear functions, transcriptional targets, release mechanisms, cellular sources, multiple functions, their interactions and potential therapeutic targeting is warranted.
Topics: Alarmins; Humans; Inflammation; Wounds and Injuries
PubMed: 29728738
DOI: 10.1007/s00068-018-0962-3 -
Frontiers in Immunology 2023The initiation of type 2 immune responses at mucosal barriers is regulated by rapidly secreted cytokines called alarmins. The alarmins IL-33, IL-25 and TSLP are mainly...
The initiation of type 2 immune responses at mucosal barriers is regulated by rapidly secreted cytokines called alarmins. The alarmins IL-33, IL-25 and TSLP are mainly secreted by stromal and epithelial cells in tissues and were linked to chronic inflammatory diseases, such as allergic lung inflammation, or to resistance against worm infections. Receptors for alarmins are expressed by a variety of immune cells, including group 2 innate lymphoid cells (ILC2s), an early source of the type 2 cytokines, such as IL-5 and IL-13, which have been linked to atopic diseases and anti-worm immunity as well. However, the precise contribution of the IL-33 receptor signals for ILC2 activation still needs to be completed due to limitations in targeting genes in ILC2. Using the newly established mouse model, we obtained specific conditional genetic ablation of the IL-33 receptor subunit ST2 in ILC2s. ST2-deficient ILC2s were unresponsive to IL-33 but not to stimulation with the alarmin IL-25. As a result of defective ST2 signals, ILC2s produced limited amounts of IL-5 and IL-13 and failed to support eosinophil homeostasis. Further, ST2-deficient ILC2s were unable to expand and promote the recruitment of eosinophils during allergic lung inflammation provoked by papain administration. During infection with , ILC2-intrinsic ST2 signals were required to mount an effective type 2 immune response against the parasite leading to higher susceptibility against worm infection in conditional knockout mice. Therefore, this study argues for a non-redundant role of cell-intrinsic ST2 signals triggering proper activation of ILC2 for initiation of type 2 immunity.
Topics: Animals; Mice; Alarmins; Cytokines; Immunity, Innate; Interleukin-1 Receptor-Like 1 Protein; Interleukin-13; Interleukin-33; Interleukin-5; Lymphocytes; Pulmonary Eosinophilia; Nippostrongylus; Strongylida Infections
PubMed: 37063913
DOI: 10.3389/fimmu.2023.1130933 -
Nature Communications Nov 2023As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is...
As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is essential to restore new T-cell production following tissue damage from environmental factors and therapeutic interventions. Here, we show the alarmin interleukin (IL) 33 is a product of Sca1 thymic mesenchyme both necessary and sufficient for thymus regeneration via a type 2 innate immune network. IL33 stimulates expansion of IL5-producing type 2 innate lymphoid cells (ILC2), which triggers a cellular switch in the intrathymic availability of IL4. This enables eosinophil production of IL4 to re-establish thymic mesenchyme prior to recovery of thymopoiesis-inducing epithelial compartments. Collectively, we identify a positive feedback mechanism of type 2 innate immunity that regulates the recovery of thymus function following tissue injury.
Topics: Interleukin-33; Alarmins; Immunity, Innate; Interleukin-4; Lymphocytes
PubMed: 37938566
DOI: 10.1038/s41467-023-43072-x -
Journal of Biomedical Science Aug 2023Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered... (Review)
Review
Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered by danger associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue. Besides protein-related DAMPs or "alarmins", numerous nucleic acid DAMPs exist in body fluids, such as cell-free nuclear and mitochondrial DNA as well as different species of extracellular RNA, collectively termed as self-extracellular nucleic acids (SENAs). Among these, microRNA, long non-coding RNAs, circular RNAs and extracellular ribosomal RNA constitute the majority of RNA-based DAMPs. Upon tissue injury, necrosis or apoptosis, such SENAs are released from neuronal, immune and other cells predominantly in association with extracellular vesicles and may be translocated to target cells where they can induce intracellular regulatory pathways in gene transcription and translation. The majority of SENA-induced signaling reactions in the brain appear to be related to neuroinflammatory processes, often causally associated with the onset or progression of the respective disease. In this review, the impact of the diverse types of SENAs on neuroinflammatory and neurodegenerative diseases will be discussed. Based on the accumulating knowledge in this field, several specific antagonistic approaches are presented that could serve as therapeutic interventions to lower the pathological outcome of the indicated brain disorders.
Topics: Humans; Nucleic Acids; Neuroinflammatory Diseases; Brain; MicroRNAs; Alarmins; Neurodegenerative Diseases
PubMed: 37550658
DOI: 10.1186/s12929-023-00954-y -
Biochimica Et Biophysica Acta.... Feb 2019The innate immune system is the first line of defense against pathogenic threats. For the early pathogen recognition and activation of cell protective mechanisms,... (Review)
Review
The innate immune system is the first line of defense against pathogenic threats. For the early pathogen recognition and activation of cell protective mechanisms, germline-encoded pattern recognition receptors (PRRs) detect characteristic and evolutionary conserved pathogen-associated molecular patterns (PAMPs). PRRs are therefore key elements in the innate immune response; in addition, they sense danger-associated molecular patterns (DAMPs) that are released by host cell molecules under pathophysiological conditions. Formyl peptide receptors (FPRs) are G-protein-coupled PRRs that respond to a surprisingly broad range of ligands, derived from both pathogens and host cells. Here, we exemplary discuss ligands in order to illustrate the wide pathophysiological relevance of the FPR signaling axis in case of e.g., chronic inflammations and to underscore its potential therapeutic value in the light of "biased agonism", a modern concept of GPCR (G-protein coupled receptors) activation. These novel insights into the GPCR receptor biochemistry will hopefully (re)stimulate FPR-related research and lead to novel strategies for the urgently needed development of drugs with pharmacologically advantageous characteristics.
Topics: Alarmins; Animals; Humans; Immune System; Immunity, Innate; Inflammation; Ligands; Mice; Pathogen-Associated Molecular Pattern Molecules; Receptors, Formyl Peptide; Receptors, Pattern Recognition; Signal Transduction
PubMed: 30521870
DOI: 10.1016/j.bbamcr.2018.11.015 -
Cells Aug 2022The innate immune system is the first line of defense against bacterial and viral infections and sterile inflammation through the recognition of pathogen-associated...
The innate immune system is the first line of defense against bacterial and viral infections and sterile inflammation through the recognition of pathogen-associated molecular patterns (PAMPs) as well as danger-associated molecular patterns (DAMPs) by pathogen-recognition receptors (PRRs), and produces proinflammatory and antiviral cytokines and chemokines [...].
Topics: Alarmins; Bacterial Infections; Cytokines; Humans; Immunity, Innate; Receptors, Pattern Recognition; Virus Diseases
PubMed: 36078113
DOI: 10.3390/cells11172705 -
European Journal of Trauma and... Aug 2020In 1994, the "danger model" argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of "strange"... (Review)
Review
In 1994, the "danger model" argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of "strange" molecules. Thus, an alternative to the "self versus non-self recognition model" has been provided. The model, which suggests that the immune system discriminates dangerous from safe molecules, has established the basis for the future designation of damage-associated molecular patterns (DAMPs), a term that was coined by Walter G. Land, Seong, and Matzinger. The pathological importance of DAMPs is barely somewhere else evident as in the posttraumatic or post-surgical inflammation and regeneration. Since DAMPs have been identified to trigger specific immune responses and inflammation, which is not necessarily detrimental but also regenerative, it still remains difficult to describe their "friend or foe" role in the posttraumatic immunogenicity and healing process. DAMPs can be used as biomarkers to indicate and/or to monitor a disease or injury severity, but they also may serve as clinically applicable parameters for optimized indication of the timing for, i.e., secondary surgeries. While experimental studies allow the detection of these biomarkers on different levels including cellular, tissue, and circulatory milieu, this is not always easily transferable to the human situation. Thus, in this review, we focus on the recent literature dealing with the pathophysiological importance of DAMPs after traumatic injury. Since dysregulated inflammation in traumatized patients always implies disturbed resolution of inflammation, so-called model of suppressing/inhibiting inducible DAMPs (SAMPs) will be very briefly introduced. Thus, an update on this topic in the field of trauma will be provided.
Topics: Alarmins; Animals; Biomarkers; Disease Models, Animal; Humans; Immune System Phenomena; Inflammation; Wounds and Injuries
PubMed: 31612270
DOI: 10.1007/s00068-019-01235-w -
Frontiers in Immunology 2021
Topics: Alarmins; Animals; Cell Plasticity; Communicable Diseases; Host-Pathogen Interactions; Humans; Inflammasomes; Inflammation; Macrophages; Pathogen-Associated Molecular Pattern Molecules; Phenotype; Signal Transduction
PubMed: 34975930
DOI: 10.3389/fimmu.2021.823023 -
Journal of Zhejiang University.... May 2019Necroptosis is a tightly regulated form of necrosis that requires the activation of receptor-interacting protein (RIP) kinases RIPK1 and RIPK3, as well as the RIPK3... (Review)
Review
Necroptosis is a tightly regulated form of necrosis that requires the activation of receptor-interacting protein (RIP) kinases RIPK1 and RIPK3, as well as the RIPK3 substrate mixed lineage kinase domain-like protein (MLKL). Because of membrane rupture, necroptotic cells release damage-associated molecular patterns (DAMPs) that evoke immune responses. Necroptosis is emerging as an important cellular response in the modulation of cancer initiation, progression, and metastasis. Necroptosis of cancer cells is considered to be an immunogenic cell death capable of activating anti-tumor immunity. Necroptosis also participates in the promotion of myeloid cell-induced adaptive immune suppression and thus contributes to oncogenesis. In addition, necroptosis of endothelial cells and tumor cells is conducive to tumor metastasis. In this review, we summarize the current knowledge of the complex role of necroptosis in cancer and discuss the potential of targeting necroptosis components for cancer therapies.
Topics: Alarmins; Animals; Apoptosis; Carcinogenesis; Cell Differentiation; Drug Resistance, Neoplasm; Endothelial Cells; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Immune System; Immunotherapy; Inflammation; Necrosis; Neoplasm Metastasis; Neoplasms; Protein Kinases; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 31090266
DOI: 10.1631/jzus.B1900160