scholarly journals Basophils Orchestrating Eosinophils’ Chemotaxis and Function in Allergic Inflammation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 895
Author(s):  
Joseena Iype ◽  
Michaela Fux
Keyword(s):  
Current Knowledge ◽  
Allergic Inflammation ◽  
Potential Interaction ◽  
Cytokines And Chemokines ◽  
New Findings ◽  
Th2 Immunity ◽  
Experimental Allergy ◽  
And Function ◽  
Inflammatory Tissue

Eosinophils are well known to contribute significantly to Th2 immunity, such as allergic inflammations. Although basophils have often not been considered in the pathogenicity of allergic dermatitis and asthma, their role in Th2 immunity has become apparent in recent years. Eosinophils and basophils are present at sites of allergic inflammations. It is therefore reasonable to speculate that these two types of granulocytes interact in vivo. In various experimental allergy models, basophils and eosinophils appear to be closely linked by directly or indirectly influencing each other since they are responsive to similar cytokines and chemokines. Indeed, basophils are shown to be the gatekeepers that are capable of regulating eosinophil entry into inflammatory tissue sites through activation-induced interactions with endothelium. However, the direct evidence that eosinophils and basophils interact is still rarely described. Nevertheless, new findings on the regulation and function of eosinophils and basophils biology reported in the last 25 years have shed some light on their potential interaction. This review will focus on the current knowledge that basophils may regulate the biology of eosinophil in atopic dermatitis and allergic asthma.

scholarly journals Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.

1996 ◽  
Vol 184 (5) ◽  
pp. 1939-1951 ◽  
Author(s):  
G Q Jia ◽  
J A Gonzalo ◽  
C Lloyd ◽  
L Kremer ◽  
L Lu ◽  
...  
Keyword(s):  
Inflammatory Reaction ◽  
Allergic Inflammation ◽  
The Novel ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Allergic Lung Inflammation ◽  
Cc Chemokines ◽  
And Function

We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP-5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP-5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation.

scholarly journals Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Wai Y. Sun ◽  
Claudine S. Bonder
Keyword(s):  
Current Knowledge ◽  
Financial Burden ◽  
Late Phase ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Racial Groups ◽  
Worldwide Population ◽  
Life Threatening

Allergic inflammation is an immune response to foreign antigens, which begins within minutes of exposure to the allergen followed by a late phase leading to chronic inflammation. Prolonged allergic inflammation manifests in diseases such as urticaria and rhino-conjunctivitis, as well as chronic asthma and life-threatening anaphylaxis. The prevalence of allergic diseases is profound with 25% of the worldwide population affected and a rising trend across all ages, gender, and racial groups. The identification and avoidance of allergens can manage this disease, but this is not always possible with triggers being common foods, prevalent air-borne particles and only extremely low levels of allergen exposure required for sensitization. Patients who are sensitive to multiple allergens require prophylactic and symptomatic treatments. Current treatments are often suboptimal and associated with adverse effects, such as the interruption of cognition, sleep cycles, and endocrine homeostasis, all of which affect quality of life and are a financial burden to society. Clearly, a better therapeutic approach for allergic diseases is required. Herein, we review the current knowledge of allergic inflammation and discuss the role of sphingolipids as potential targets to regulate inflammatory development in vivo and in humans. We also discuss the benefits and risks of using sphingolipid inhibitors.

scholarly journals Highly Selective Cleavage of TH2-Promoting Cytokines by the Human and the Mouse Mast Cell Tryptases, Indicating a Potent Negative Feedback Loop on TH2 Immunity

2019 ◽  
Vol 20 (20) ◽  
pp. 5147 ◽  
Author(s):  
Zhirong Fu ◽  
Srinivas Akula ◽  
Michael Thorpe ◽  
Lars Hellman
Keyword(s):  
Negative Feedback ◽  
Feedback Loop ◽  
Regulatory Function ◽  
Negative Feedback Loop ◽  
Cytokines And Chemokines ◽  
Th2 Immunity ◽  
Strict Specificity ◽  
Mouse Mast Cell ◽  
Regulatory Functions

Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and the environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is tryptase. To look deeper into the question of their in vivo targets, we have analyzed the activity of the human MC tryptase on 69 different human cytokines and chemokines, and the activity of the mouse tryptase (mMCP-6) on 56 mouse cytokines and chemokines. These enzymes were found to be remarkably restrictive in their cleavage of these potential targets. Only five were efficiently cleaved by the human tryptase: TSLP, IL-21, MCP3, MIP-3b, and eotaxin. This strict specificity indicates a regulatory function of these proteases and not primarily as unspecific degrading enzymes. We recently showed that the human MC chymase also had a relatively strict specificity, indicating that both of these proteases have regulatory functions. One of the most interesting regulatory functions may involve controlling excessive TH2-mediated inflammation by cleaving several of the most important TH2-promoting inflammatory cytokines, including IL-18, IL-33, TSLP, IL-15, and IL-21, indicating a potent negative feedback loop on TH2 immunity.

scholarly journals Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice

Blood ◽  
2011 ◽  
Vol 118 (26) ◽  
pp. 6930-6938 ◽  
Author(s):  
Jennifer N. Lilla ◽  
Ching-Cheng Chen ◽  
Kaori Mukai ◽  
Maya J. BenBarak ◽  
Christopher B. Franco ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Genetic Manipulation ◽  
Allergic Inflammation ◽  
Myeloid Cell ◽  
Hematopoietic Cell ◽  
Cell Populations ◽  
And Function

Abstract It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1fl/fl mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1fl/fl mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell- and IgE-dependent passive cutaneous anaphylaxis (except at sites engrafted with in vitro–derived mast cells) and a basophil- and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1fl/fl mice may be useful in analyzing the roles of mast cells and basophils in health and disease.

scholarly journals The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Marta Boccazzi ◽  
Juliette Van Steenwinckel ◽  
Anne-Laure Schang ◽  
Valérie Faivre ◽  
Tifenn Le Charpentier ◽  
...  
Keyword(s):  
White Matter ◽  
Primary Cultures ◽  
White Matter Injury ◽  
Poly I:C ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Preterm Born ◽  
And Function

AbstractA leading cause of preterm birth is the exposure to systemic inflammation (maternal/fetal infection), which leads to neuroinflammation and white matter injury (WMI). A wide range of cytokines and chemokines are expressed and upregulated in oligodendrocytes (OLs) in response to inflammation and numerous reports show that OLs express several receptors for immune related molecules, which enable them to sense inflammation and to react. However, the role of OL immune response in WMI is unclear. Here, we focus our study on toll-like receptor-3 (TLR3) that is activated by double-strand RNA (dsRNA) and promotes neuroinflammation. Despite its importance, its expression and role in OLs remain unclear. We used an in vivo mouse model, which mimics inflammation-mediated WMI of preterm born infants consisting of intraperitoneal injection of IL-1β from P1 to P5. In the IL-1β-treated animals, we observed the upregulation of Tlr3, IL-1β, IFN-β, Ccl2, and Cxcl10 in both PDGFRα+ and O4+ sorted cells. This upregulation was higher in O4+ immature OLs (immOLs) as compared to PDGFRα+ OL precursor cells (OPCs), suggesting a different sensitivity to neuroinflammation. These observations were confirmed in OL primary cultures: cells treated with TLR3 agonist Poly(I:C) during differentiation showed a stronger upregulation of Ccl2 and Cxcl10 compared to cells treated during proliferation and led to decreased expression of myelin genes. Finally, OLs were able to modulate microglia phenotype and function depending on their maturation state as assessed by qPCR using validated markers for immunomodulatory, proinflammatory, and anti-inflammatory phenotypes and by phagocytosis and morphological analysis. These results show that during inflammation the response of OLs can play an autonomous role in blocking their own differentiation: in addition, the immune activation of OLs may play an important role in shaping the response of microglia during inflammation.

scholarly journals Large-Scale Computational Discovery of Binding Motifs in tRNA Fragments

2021 ◽  
Vol 8 ◽  
Author(s):  
Lingyu Guan ◽  
Vincent Lam ◽  
Andrey Grigoriev
Keyword(s):  
Large Scale ◽  
Potential Interaction ◽  
Binding Motifs ◽  
Argonaute Proteins ◽  
Potential Binding ◽  
Computational Discovery ◽  
And Function ◽  
Trna Halves ◽  
Binding Mechanisms

Accumulating evidence has suggested that tRNA-derived fragments (tRFs) could be loaded to Argonaute proteins and function as regulatory small RNAs. However, their mode of action remains largely unknown, and investigations of their binding mechanisms have been limited, revealing little more than microRNA-like seed regions in a handful of tRFs and a few targets. Here, we identified such regions of potential interaction on a larger scale, using in vivo formed hybrids of guides and targets in crosslinked chimeric reads in two orientations. We considered “forward pairs” (with guides located on the 5′ ends and targets on the 3′ ends of hybrids) and “reverse pairs” (opposite orientation) and compared them as independent sets of biological constructs. We observed intriguing differences between the two chimera orientations, including the paucity of tRNA halves and abundance of polyT-containing targets in forward pairs. We found a total of 197 quality-ranked motifs supported by ∼120,000 tRF–mRNA chimeras, with 103 interacting motifs common in forward and reverse pairs. By analyzing T→C conversions in human and mouse PAR-CLIP datasets, we detected Argonaute crosslinking sites in tRFs, conserved across species. We proposed a novel model connecting the formation of asymmetric pairs in two sets to the potential binding mechanisms of tRFs, involving the identified interaction motifs and crosslinking sites to Argonaute proteins. Our results suggest the way forward for further experimental elucidation of tRF-binding mechanisms.

scholarly journals Unexpected Role of Matrix Gla Protein in Osteoclasts: Inhibiting Osteoclast Differentiation and Bone Resorption

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Yan Zhang ◽  
Liting Zhao ◽  
Naining Wang ◽  
Jing Li ◽  
Fang He ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Nuclear Translocation ◽  
Current Knowledge ◽  
Bone Matrix ◽  
Osteoclast Differentiation ◽  
Matrix Gla Protein ◽  
Activated T Cells ◽  
And Function

ABSTRACT Matrix Gla protein (MGP) is an extracellular protein responsible for inhibiting mineralization. MGP inhibits osteoblast mineralization and bone formation by regulating the deposition of bone matrix. However, Mgp–/– mice display an osteopenic phenotype. To explain this contradiction, we investigated the role of MGP in osteoclastogenesis, the other side of bone remodeling. We found that MGP expression is markedly increased by osteoclastic commitment. Osteoclast differentiation and bone resorption are accelerated by MGP depletion while suppressed by MGP overexpression. The in vivo results confirmed its inhibitory role in osteoclastogenesis by the administration of Cre-dependent FLEX-On recombinant MGP-AAV to LysM Cre mice. Furthermore, we found that the expression and nuclear translocation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), are under the control of MGP. MGP loss results in elevation of intracellular Ca2+ flux. Vitronectin-induced activation of Src/Rac1 is magnified in the absence of MGP but reduced when MGP is overexpressed. Inhibition of Src activation or NFATc1 nuclear import rescues the increased osteoclastogenesis induced by MGP deficiency. These observations (i) establish, for the first time to our knowledge, that MGP plays an essential role in osteoclast differentiation and function, (ii) enrich the current knowledge of MGP function, and (iii) indicate the potential of MGP as a therapeutic target for low-bone-mass disorders.

scholarly journals Immunoregulatory peptides in bovine milk

2000 ◽  
Vol 84 (S1) ◽  
pp. 111-117 ◽  
Author(s):  
Harsharnjit S. Gill ◽  
F. Doull ◽  
K. J. Rutherfurd ◽  
M. L. Cross
Keyword(s):  
Immune Function ◽  
Human Health ◽  
De Novo ◽  
Current Knowledge ◽  
Bovine Milk ◽  
Milk Proteins ◽  
Immunological Responses ◽  
Probiotic Lactic Acid Bacteria ◽  
And Function

Bovine milk is known to contain a number of peptide fractions that can affect immune function. The vast majority of immunoregulatory peptides that have been characterised are hydrolysate derivatives of major milk proteins. Recent research has also indicated that the metabolic activity of probiotic lactic acid bacteria can generate de novo immunoregulatory peptides from milk, via enzymatic degradation of parent milk protein molecules. In contrast, relatively little is known of endogenous, preformed immunoregulatory peptides in milk that may be relevant to modulating human health. The natural in vivo role of preformed and enzymatically derived peptides is likely to be one of regulation of the neonatal (bovine) gastrointestinal tract immune system, in order to modulate immune function with respect to the development of immunocompetence and avoidance of undesirable immunological responses (e.g. tolerance, and hypersensitivity to nutrients). There is scope for the further characterisation of both the origin and function of milk-derived immunoregulatory peptides, so that their potential to influence human health can be fully appraised. This review highlights our current knowledge of milk-derived immunoregulatory peptides, and outlines areas that are of relevance for further research.

scholarly journals Comparative analyses of long non-coding RNA profiles in vivo in cystic fibrosis lung airway and parenchyma tissues

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Parameet Kumar ◽  
Chaitali Sen ◽  
Kathryn Peters ◽  
Raymond A. Frizzell ◽  
Roopa Biswas
Keyword(s):  
Cystic Fibrosis ◽  
Lung Parenchyma ◽  
Differentially Expressed ◽  
Cellular Processes ◽  
Cytokines And Chemokines ◽  
Non Coding Rna ◽  
Key Factor ◽  
New Perspective ◽  
And Function

Abstract Background Recent advances in the functional analyses of endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs), have provided a new perspective on the crucial roles of RNA in gene regulation. Consequently, LncRNA deregulation is a key factor in various diseases, including pulmonary disorders like Cystic Fibrosis (CF). CF is the most common life limiting recessive disease in the U.S., and is due to mutations in the CFTR gene. CF mutations, of which the most common is F508del-CFTR, prevents correct folding, trafficking and function of the mutant CFTR protein and is further manifested by the hyper-expression of pro-inflammatory cytokines and chemokines into the airway lumen leading to bronchiectasis and culminating in lung destruction. Methods Here we report a distinct LncRNA signature and corresponding mRNAs that distinguishes CF lung (airway and parenchyma) tissues from matched non-CF controls (n = 4 each group), generated by microarray specific for LncRNAs which includes corresponding mRNA expressions. In silico analyses of the cellular processes that are impacted by these LncRNAs was performed using Gene Ontology (GO). A selected subset of LncRNAs were validated by quantitative real-time PCR. Results We have identified 636 LncRNAs differentially expressed in CF airway epithelium and 1974 in CF lung parenchyma compared to matched non-CF controls (fold change ≥2, p < 0.05), majority of which (> 50%) are intergenic. Interestingly, 15 of these differentially expressed LncRNAs and 9 coding mRNAs are common to airway and parenchyma tissues. GO analyses indicates that signaling pathways and cell membrane functions are significantly affected by the alteration in LncRNA expressions in CF lung tissues. Seven of the differentially expressed LncRNAs, exhibit similar expression trends in CFBE41o- compared to control cells. Conclusion Understanding the mechanisms by which these LncRNAs regulate CF disease phenotype will help develop novel therapeutic targets for CF and related pulmonary diseases, such as COPD and Asthma.

scholarly journals Type III secretion systems: the bacterial flagellum and the injectisome

2015 ◽  
Vol 370 (1679) ◽  
pp. 20150020 ◽  
Author(s):  
Andreas Diepold ◽  
Judith P. Armitage
Keyword(s):  
Type Iii Secretion ◽  
Current Knowledge ◽  
Electron Tomography ◽  
Secretion Systems ◽  
Bacterial Flagellum ◽  
Type Iii ◽  
New Findings ◽  
Potential Applications ◽  
Flagellar Filament

The flagellum and the injectisome are two of the most complex and fascinating bacterial nanomachines. At their core, they share a type III secretion system (T3SS), a transmembrane export complex that forms the extracellular appendages, the flagellar filament and the injectisome needle. Recent advances, combining structural biology, cryo-electron tomography, molecular genetics, in vivo imaging, bioinformatics and biophysics, have greatly increased our understanding of the T3SS, especially the structure of its transmembrane and cytosolic components, the transcriptional, post-transcriptional and functional regulation and the remarkable adaptivity of the system. This review aims to integrate these new findings into our current knowledge of the evolution, function, regulation and dynamics of the T3SS, and to highlight commonalities and differences between the two systems, as well as their potential applications.

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