Immune-Mediated Mechanisms in Cofactor-Dependent Food Allergy and Anaphylaxis: Effect of Cofactors in Basophils and Mast Cells

Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction or tolerance. With cofactors, reactions become more severe and/or have a lower allergen threshold. Cofactors are present in up to 58% of food anaphylaxis (FAn). Exercise, NSAIDs, and alcohol are the most frequently described, although the underlying mechanisms are poorly known. Several hypotheses have suggested the influence of these cofactors on basophils and mast cells (MCs). Exercise has been suggested to enhance MC activation by increasing plasma osmolarity, redistributing blood flow, and activating adenosine and eicosanoid metabolism. NSAIDs’ cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E2 (PGE2) production. Indeed, overexpression of adenosine receptor 3 (A3) gene has been described in NSAID-dependent FAn; A3 activation potentiates FcϵRI-induced MC degranulation. Finally, alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and also with and increase of extracellular adenosine by inhibition of its uptake. However, most of these mechanisms have limited evidence, and further studies are urgently needed. In conclusion, the study of the immune-related mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent.

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Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

Cell and Tissue Research ◽

10.1007/s00441-021-03499-4 ◽

2021 ◽

Author(s):

Melissa C. Stein ◽

Fabian Braun ◽

Christian F. Krebs ◽

Madeleine J. Bunders

Keyword(s):

Kidney Diseases ◽

Three Dimensional ◽

Renal Tissue ◽

Chronic Kidney Diseases ◽

Immune Mediated ◽

Primary Epithelial Cell ◽

Challenges And Opportunities ◽

Underlying Mechanisms ◽

Global Population

AbstractAcute and chronic kidney diseases are major contributors to morbidity and mortality in the global population. Many nephropathies are considered to be immune-mediated with dysregulated immune responses playing an important role in the pathogenesis. At present, targeted approaches for many kidney diseases are still lacking, as the underlying mechanisms remain insufficiently understood. With the recent development of organoids—a three-dimensional, multicellular culture system, which recapitulates important aspects of human tissues—new opportunities to investigate interactions between renal cells and immune cells in the pathogenesis of kidney diseases arise. To date, kidney organoid systems, which reflect the structure and closer resemble critical aspects of the organ, have been established. Here, we highlight the recent advances in the development of kidney organoid models, including pluripotent stem cell-derived kidney organoids and primary epithelial cell-based tubuloids. The employment and further required advances of current organoid models are discussed to investigate the role of the immune system in renal tissue development, regeneration, and inflammation to identify targets for the development of novel therapeutic approaches of immune-mediated kidney diseases.

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

Cells ◽

10.3390/cells10071615 ◽

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.

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Chia oil prevents chemical and immune-mediated inflammatory responses in mice: Evidence for the underlying mechanisms

Food Research International ◽

10.1016/j.foodres.2021.110703 ◽

2021 ◽

Vol 149 ◽

pp. 110703

Author(s):

Juliana Cavalli ◽

Mariana A. Freitas ◽

Elaine C.D. Gonçalves ◽

Guilherme P. Fadanni ◽

Adara A. Santos ◽

...

Keyword(s):

Inflammatory Responses ◽

Immune Mediated ◽

Underlying Mechanisms ◽

Chia Oil

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5030623 Methods for increasing extracellular adenosine and for stabilizing mast cells

Biotechnology Advances ◽

10.1016/0734-9750(91)90992-5 ◽

1991 ◽

Vol 9 (3) ◽

pp. 469

Keyword(s):

Mast Cells ◽

Extracellular Adenosine

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The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

Science Signaling ◽

10.1126/scisignal.aao4354 ◽

2018 ◽

Vol 11 (556) ◽

pp. eaao4354 ◽

Cited By ~ 1

Author(s):

Ivana Halova ◽

Monika Bambouskova ◽

Lubica Draberova ◽

Viktor Bugajev ◽

Petr Draber

Keyword(s):

Mast Cell ◽

Mast Cells ◽

T Cell Activation ◽

Cell Activation ◽

Adaptor Protein ◽

Prostaglandin E ◽

Dependent Manner ◽

And Function ◽

Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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Prostaglandin E2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 channels

Respiratory Research ◽

10.1186/s12931-021-01889-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Al-Shaimaa A. Al-Kandery ◽

Muddanna S. Rao ◽

Ahmed Z. El-Hashim

Keyword(s):

Citric Acid ◽

Nucleus Tractus Solitarius ◽

Whole Body ◽

Prostaglandin E ◽

Cough Reflex ◽

Trpv1 Antagonist ◽

Underlying Mechanisms ◽

Set Up ◽

Guinea Pig Model ◽

Ep3 Receptor

Abstract Background Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E2 (PGE2), have been implicated in both peripheral induction and sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE2 can sensitize the cough reflex via central actions and, if so, via which mechanisms. Methods All drugs were administered by intracerebroventricular (i.c.v.) route and whole-body plethysmograph set-up was used for both induction, using aerosolized citric acid (0.2 M), and recording of cough. Immunohistochemistry was performed to confirm the expression of NaV 1.8 channels in the nucleus tractus solitarius (nTS). Results We show that both PGE2 and the non-selective EP1/EP3 agonist, sulprostone, dose-dependently enhanced the citric acid-induced cough (P ≤ 0.001, P ≤ 0.01, respectively). Pretreatment with the EP1 antagonist, ONO-8130, did not affect the sulprostone-induced cough sensitization, whilst the EP3 antagonist, L-798,106, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, treatment with either the EP2 agonist, butaprost or the EP4 agonist, L-902,688, had no effect on cough sensitization. Additionally, pretreatment with either the TRPV1 antagonist, JNJ-17203212 or the TRPA1 antagonist, HC-030031, alone or in combination, nor with the NaV 1.1, 1.2, 1.3, 1.4, 1.6 and 1.7 channel blocker, tetrodotoxin, had any effect on the cough. In contrast, pretreatment with the NaV 1.8 antagonist, A-803467, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, NaV 1.8 channels were shown to be expressed in the nTS. Conclusion Collectively, our findings show that PGE2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 but independently of TRPV1,TRPA1 and TTX-sensitive sodium channel activation. These results indicate that PGE2 plays an important role in central sensitization of the cough reflex and suggest that central EP3 receptors and/or NaVv 1.8 channels may represent novel antitussive molecular targets. Graphical Abstract

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Assessment of Expression of SOCS Genes in Acquired Immune-Mediated Polyneuropathies

Frontiers in Immunology ◽

10.3389/fimmu.2021.712859 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mohammad Taheri ◽

Somayeh Sangseifid ◽

Pariya Shahani ◽

Mohammad Mahdi Eftekharian ◽

Shahram Arsang-Jang ◽

...

Keyword(s):

Specific Pattern ◽

Bayesian Regression ◽

Cytokine Signaling ◽

Control Group ◽

Operating Characteristics ◽

Mean Values ◽

Immune Mediated ◽

Male Patients ◽

Underlying Mechanisms ◽

And Control

Acquired immune-mediated polyneuropathies are classified to some subtypes among them are acute and chronic inflammatory demyelinating polyradiculoneuropathies (AIDP and CIDP). These two conditions share some common signs and underlying mechanisms. Based on the roles of Suppressor of cytokine signaling (SOCS) genes in the modulation of immune system reactions, these genes might be involved in the pathogenesis of these conditions. We evaluated expression of SOCS1-3 and SOCS5 genes in the leukocytes of 32 cases of CIDP, 19 cases of AIDP and 40 age- and sex-matched controls using real time PCR method. The Bayesian regression model was used to estimate differences in mean values of genes expressions between cases and control group. Expression levels of SOCS1 and SOCS2 were significantly lower in male patients compared with controls. This sex-specific pattern was also observed for SOCS3 down-regulation. Based on the area under curve values in Receiver Operating Characteristics (ROC) curve, diagnostic powers of SOCS1, SOCS2, SOCS3 and SOCS5 genes in the mentioned disorder were 0.61, 0.73, 0.68 and 0.58, respectively. Expression of none of genes was correlated with age of enrolled cases. The current study shows evidences for participation of SOCS genes in the pathophysiology of acquired immune-mediated polyneuropathies.

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Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice

Journal of Clinical Medicine ◽

10.3390/jcm8050663 ◽

2019 ◽

Vol 8 (5) ◽

pp. 663 ◽

Cited By ~ 3

Author(s):

Eva Nüsken ◽

Eva-Maria Turnwald ◽

Gregor Fink ◽

Jenny Voggel ◽

Christopher Yosy ◽

...

Keyword(s):

High Fat Diet ◽

Maternal Obesity ◽

Laser Microdissection ◽

Kidney Tissue ◽

Standard Diet ◽

High Fat ◽

Proteomic Screen ◽

Eicosanoid Metabolism ◽

Associated Conditions ◽

Underlying Mechanisms

There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or high fat diet (HFD) from weaning until mating and during pregnancy. Half of the dams from both groups were treated with metformin ((M), 380 mg/kg), resulting in four experimental groups (SD, SD-M, HFD, HFD-M). Caesarean section was performed on gestational day 18.5. Fetal kidney tissue was isolated from cryo-slices using laser microdissection methods and a proteomic screen was performed. For single proteins, a fold change ≥1.5 and q-value <0.05 were considered to be statistically significant. Interestingly, HFD versus SD had a larger effect on the proteome of fetal kidneys (56 proteins affected; interaction clusters shown for proteins concerning transcription/translation, mitochondrial processes, eicosanoid metabolism, H2S-synthesis and membrane remodeling) than metformin exposure in either SD (29 proteins affected; clusters shown for proteins involved in transcription/translation) or HFD (6 proteins affected; no cluster). By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.

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