Pathogenic CCR6+ dendritic cells in the skin lesions of discoid lupus patients: a role for damage-associated molecular patterns

2013 ◽  
Vol 23 (2) ◽  
pp. 169-182 ◽  
Author(s):  
Aniela Méndez-Reguera ◽  
Gibrán Pérez-Montesinos ◽  
Marcela Alcántara-Hernández ◽  
Virginia Martínez-Estrada ◽  
Jorge Rafael Cazarin-Barrientos ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Skin Lesions ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

scholarly journals Psoriasis and Antimicrobial Peptides

2020 ◽  
Vol 21 (18) ◽  
pp. 6791 ◽  
Author(s):  
Toshiya Takahashi ◽  
Kenshi Yamasaki
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Antimicrobial Peptides ◽  
Psoriatic Skin ◽  
Myeloid Dendritic Cells ◽  
Dna And Rna ◽  
Systemic Inflammatory Disease ◽  
Th1 Cytokines ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Psoriasis is a systemic inflammatory disease caused by crosstalk between various cells such as T cells, neutrophils, dendritic cells, and keratinocytes. Antimicrobial peptides (AMPs) such as β-defensin, S100, and cathelicidin are secreted from these cells and activate the innate immune system through various mechanisms to induce inflammation, thus participating in the pathogenesis of psoriasis. In particular, these antimicrobial peptides enhance the binding of damage-associated molecular patterns such as self-DNA and self-RNA to their receptors and promote the secretion of interferon from activated plasmacytoid dendritic cells and keratinocytes to promote inflammation in psoriasis. Neutrophil extracellular traps (NETs), complexes of self-DNA and proteins including LL-37 released from neutrophils in psoriatic skin, induce Th17. Activated myeloid dendritic cells secrete a mass of inflammatory cytokines such as IL-12 and IL-23 in psoriasis, which is indispensable for the proliferation and survival of T cells that produce IL-17. AMPs enhance the production of some of Th17 and Th1 cytokines and modulate receptors and cellular signaling in psoriasis. Inflammation induced by DAMPs, including self-DNA and RNA released due to microinjuries or scratches, and the enhanced recognition of DAMPs by AMPs, may be involved in the mechanism underlying the Köbner phenomenon in psoriasis.

scholarly journals Honokiol-enhanced cytotoxic T lymphocyte activity against cholangiocarcinoma cells mediated by dendritic cells pulsed with damage-associated molecular patterns

2019 ◽  
Vol 25 (29) ◽  
pp. 3941-3955 ◽  
Author(s):  
Arunya Jiraviriyakul ◽  
Worawat Songjang ◽  
Pongsathorn Kaewthet ◽  
Phachsita Tanawatkitichai ◽  
Punyapat Bayan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Activity ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

scholarly journals Release mechanisms of major DAMPs

APOPTOSIS ◽  
2021 ◽  
Vol 26 (3-4) ◽  
pp. 152-162
Author(s):  
Atsushi Murao ◽  
Monowar Aziz ◽  
Haichao Wang ◽  
Max Brenner ◽  
Ping Wang
Keyword(s):  
Rna Binding ◽  
High Mobility ◽  
Live Cells ◽  
Membrane Channel ◽  
Membrane Rupture ◽  
Underlying Mechanisms ◽  
Shock Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Secretory Lysosomes

AbstractDamage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

scholarly journals Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Mitochondrial Content ◽  
Sorting Nexin ◽  
Inflammatory Conditions ◽  
Selective Targeting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Insight Into

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

scholarly journals Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2566
Author(s):  
María Julia Lamberti ◽  
Annunziata Nigro ◽  
Vincenzo Casolaro ◽  
Natalia Belén Rumie Vittar ◽  
Jessica Dal Col
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Current Status ◽  
Immunogenic Cell Death ◽  
Basal Expression ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

scholarly journals Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1615
Author(s):  
Zhongwei Zhang ◽  
Yosuke Kurashima
Keyword(s):  
Mast Cells ◽  
Chronic Inflammation ◽  
Regulatory Function ◽  
Type I ◽  
Allergic Reactions ◽  
Novel Approach ◽  
Molecular Patterns ◽  
Regulatory Functions ◽  
Damage Associated Molecular Patterns ◽  
Two Sides

It is well known that mast cells (MCs) initiate type I allergic reactions and inflammation in a quick response to the various stimulants, including—but not limited to—allergens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). MCs highly express receptors of these ligands and proteases (e.g., tryptase, chymase) and cytokines (TNF), and other granular components (e.g., histamine and serotonin) and aggravate the allergic reaction and inflammation. On the other hand, accumulated evidence has revealed that MCs also possess immune-regulatory functions, suppressing chronic inflammation and allergic reactions on some occasions. IL-2 and IL-10 released from MCs inhibit excessive immune responses. Recently, it has been revealed that allergen immunotherapy modulates the function of MCs from their allergic function to their regulatory function to suppress allergic reactions. This evidence suggests the possibility that manipulation of MCs functions will result in a novel approach to the treatment of various MCs-mediated diseases.

scholarly journals Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weng Sheng Kong ◽  
Naohiro Tsuyama ◽  
Hiroko Inoue ◽  
Yun Guo ◽  
Sho Mokuda ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Atopic Dermatitis ◽  
Breast Milk ◽  
Saturated Fatty Acids ◽  
Lymphoid Cells ◽  
Interleukin 17 ◽  
Immune System Development ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Long Chain

AbstractBreastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother’s milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.

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