Field Of Inflammation Research Articles

Lysophosphatidylcholine Acyltransferase 2 Contributes to Increased Allergic and Irritant Inflammation in Mice.

Platelet-activating factor (PAF) is an important chemical mediator in the field of inflammation, but its function in the skin is unclear. To unravel the role of PAF, we focused on lysophosphatidylcholine acyltransferase 2 (LPCAT2 also called LPLAT9), a biosynthetic enzyme involved in PAF production, and investigated the role of PAF in allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). We measured the amount of PAF in the skin and investigated the ear swelling responses and leukocyte infiltration into the skin following the application of 2,4,6-trinitro-1-chlorobenzene (TNCB) or croton oil in wild-type (WT) and LPCAT2 knockout (LPCAT2-KO) mice. The amount of PAF was increased in the skin of WT mice after TNCB or croton oil application but not detected in LPCAT2-KO mice. The ear swelling response was decreased in LPCAT2-KO mice compared with that in WT mice. In the ACD model, the numbers of lymphocytes, eosinophils, macrophages, mast cells and neutrophils were smaller in LPCAT2-KO mice than in WT mice. In the ICD model, the ear swelling response was also decreased in LPCAT2-KO mice compared with that in WT mice. When double staining of each inflammatory cell type and LPCAT2 was performed in ACD tissue, marked co-staining of the eosinophil marker and LPCAT2 was observed. In addition, LPCAT2 expression was observed in the epidermis. These results indicate that PAF is involved in the infiltration of several cell types into the sites of allergic and non-allergic skin inflammation. Furthermore, eosinophils and keratinocytes are primarily responsible for PAF production in skin inflammation.

Unlocking the potential: unveiling tyrphostins with Michael-reactive cyanoacrylate motif as promising inhibitors of human 5-lipoxygenase

Human 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes, mediators of the innate immune system that also play an important role in inflammatory diseases and cancer. In this study, we present compounds, containing a Michael-reactive cyanoacrylate moiety as potent inhibitors of 5-LO. Representatives of the tyrosine kinase inhibitor family called tyrphostins, structurally related to known 5-LO inhibitors, were screened for their 5-LO inhibitory properties using recombinant human 5-LO, intact human PMNL (polymorphonuclear leukocytes), and PMNL homogenates. Their mode of action was characterized by the addition of glutathione, using a fourfold cysteine 5-LO mutant and mass spectrometry analysis. SAR studies revealed several members of the tyrphostin family containing a Michael-reactive cyanoacrylate to efficiently inhibit 5-LO. We identified degrasyn (IC50 0.11 µM), tyrphostin A9 (IC50 0.8 µM), AG879 (IC50 78 nM), and AG556 (IC50 64 nM) as potent 5-LO inhibitors. Mass spectrometry analysis revealed that degrasyn and AG556 covalently bound to up to four cysteines, including C416 and/or C418 which surround the substrate entry site. Furthermore, the 5-LO inhibitory effect of degrasyn was remarkably impaired by the addition of glutathione or by the mutation of cysteines to serines at the surface of 5-LO. We successfully identified several tyrphostins as potent inhibitors of human 5-LO. Degrasyn and AG556 were able to covalently bind to 5-LO via their cyanoacrylate moiety. This provides a promising mechanism for targeting 5-LO by Michael acceptors, leading to new therapeutic opportunities in the field of inflammation and cancer.

Carotenoids from cyanobacteria modulate iNOS and inhibit the production of inflammatory mediators: Promising agents for the treatment of inflammatory conditions

Cyanobacteria are green multiproduct refineries of increasing interest for different industrial prospects. In this work, eleven cyanobacteria strains isolated from the Cape Verde archipelago were explored for their biotechnological applications in the field of inflammation. A biorefinery approach was employed to produce carotenoid-targeted extracts, further profiled by HPLC-PDA and explored for their ability to i) scavenge important physiological free radicals of oxygen (superoxide anion radical, O2•-) and nitrogen (nitric oxide, •NO) involved in the inflammatory process ii) slow-down post-inflammatory hyperpigmentation and iii) modulate the activity of inflammatory cytokine-producing enzymes, in enzymatic and cell systems comprising RAW 264.7 cells. The studied strains turned out to be important carotenoid producers (70.47–186.71 μg mg−1dry extract), mainly represented by β-carotene and zeaxanthin. The targeted-extracts stood-out for their potential to slow-down the inflammatory process through a multitarget approach: scavenging •NO and O2•-, reducing inflammatory cytokines production through lipoxygenase inhibition, and modulating the inducible nitric oxide synthase in LPS-stimulated RAW 264.7 cells, with strains of the order Nodosilineales revealing to be worth of further biotechnological exploitation.

Inflammation in Health and Disease: Novel Therapeutic Approaches

Inflammation, which is regarded as an innate immune mechanism, is a part of the intricate biological reactions of a tissue to injury that shield the organ by eliminating harmful stimuli and starting the healing process. The majority of non-steroidal anti- inflammatory medications on the market work well for inflammatory diseases. Several compounds that disrupt the inflammatory response have also been identified in Indian Medicinal Plants (IMP). The multitude of side effects associated with the anti-inflammatory medications now on the market has a negative impact on human well-being. Advent of novel anti-inflammatory therapies such as herbal preparations, recent developments in the use of bioactive ingredients from herbal remedies to treat osteoarthritis and in the application of synthetic COX-2 inhibitors, chitosan as a therapy for oral mucosal irritation, improvement in the medication used to treat acute pancreatitis, extracellular vesicles from mesenchymal cells for the therapy of inflammation, oral colonic drug delivery methods for treating inflammatory bowel disease and combined targeting therapy for inflammatory bowel management will not only effectively manage the inflammation and its associated disorders but also helps to significantly improve the quality of life. Hence the current review reveals the recent advances in the field of inflammation and anti-inflammatory activity in detail.

Introduction. - In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxid

Introduction. - In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body's ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis. Aim. - Evaluate the literature about Inflammation from the basic to the clinical. Methodology. - Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed. Results. - Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in the patients. While in the other, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically. Conclusion. - That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.

Correlations between IL-36 family cytokines in peripheral blood and subjective and objective assessment results in patients with allergic rhinitis

BackgroundInterleukin (IL)-36 family cytokines have received increasing attention, especially in the fields of inflammation and immunity research. However, whether IL-36 family cytokine levels are correlated with the results of the assessment of allergic rhinitis (AR) and affect the severity of AR remains unknown. Therefore, this study aimed to investigate the correlations between IL-36 family cytokine levels and subjective and objective assessment results and to further analyze the possible mechanisms of IL-36 family cytokines in the development of AR.MethodsAn enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of the IL-36 family cytokines IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 in the peripheral blood of patients with AR. The condition of patients with AR was assessed by 22-item sino-nasal outcome test (SNOT-22) score, visual analogue scale (VAS) scores for disease severity, and serum inhalant allergen immunoglobulin E (IgE) detection. Correlations between IL-36 family cytokine levels and subjective and objective assessment results in patients with AR were analyzed.ResultsThe concentration of IL-36α in the peripheral blood of patients with AR was the highest, and the concentration of IL-36β was the lowest. The concentration of IL-36α was higher in juvenile patients than in adult patients, and there was a difference in the IL-36Ra level between the perennial allergen group and the seasonal allergen group. There was a positive correlation between IL-36α level and IL-36γ level, IL-36γ level and IL-36Ra level, and IL-36Ra level and IL-38 level, and IL-36β level was positively correlated with IL-36Ra and IL-38 levels, respectively. IL-36α level was positively correlated with VAS score for nasal congestion symptom. IL-36β level was positively correlated with the total VAS score for ocular symptoms and VAS scores for ocular itching and eye pain symptoms. However, there was no correlation between the levels of all cytokines in IL-36 family and SNOT-22 score, the number of positive inhaled allergens, or the highest positive intensity of allergen specific immunoglobulin E (sIgE).ConclusionPeripheral blood IL-36 family cytokines play an important role in AR, and the concentrations of IL-36α and IL-36β were related to the severity of symptoms in patients with AR.

Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.

Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder. Our review will predominantly focus on neuroinflammation and systemic immune imbalance in ALS and FTD, which have recently been highlighted as novel therapeutic targets. A common mechanism of most ALS and ~50% of FTD patients is dysregulation of TAR DNA-binding protein 43 (TDP-43), an RNA/DNA-binding protein, which becomes depleted from the nucleus and forms cytoplasmic aggregates in neurons and glia. This, in turn, via both gain and loss of function events, alters a variety of TDP-43-mediated cellular events. Experimental attempts to target TDP-43 aggregates or manipulate crosstalk in the context of inflammation will be discussed. Targeting inflammation, and the immune system in general, is of particular interest because of the high plasticity of immune cells compared to neurons.

Neutrophils and their friends.

Neutrophils and their friends.

New frontiers in inflammation: from translational research to clinic (information about the 15th World Congress on Inflammation (WCI2022)).

The following provides a summary of the 15th World Congress on Inflammation (WCI2022), which took place in Rome (Italy) from June 5 to 8, 2022. Presented are the main trends and most promising research developments in the field of inflammation, including identification of cellular and molecular mechanisms and investigation of new pathogenetic pathways, target molecules, genetic mechanisms, and new therapeutic strategies. In addition, described are the primary areas of research engaged in by leading scientific groups and national societies from various countries in the field of inflammatory pathology mechanisms.

Новые рубежи изучения воспаления: от трансляционных исследований к клинике (Информация о 15-м Всемирном конгрессе по воспалению (WCI2022)

Information is provided on the 15th World Congress on Inflammation (WCI2022), which took place in Rome (Italy) from June 5 to 8, 2022. Presented main trends and the most promising directions for the development of research in the field of inflammation, including the investigations of new pathogenetic pathways, identification of cellular and molecular mechanisms, target molecules, genetic mechanisms, and new therapeutic strategies. The directions of research by leading scientific groups and national societies of various countries on the find of the mechanisms of inflammatory pathology development are described.

PKM2 regulates cigarette smoke-induced airway inflammation and epithelial-to-mesenchymal transition via modulating PINK1/Parkin-mediated mitophagy

Cigarette smoke (CS) mediates inflammation and epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, contributing to airway remodeling in chronic obstructive pulmonary disease (COPD). Cross-talk between metabolic pathways and cell signaling has emerged as an important focus of research in the field of inflammation. Here, we established in vitro and in vivo models of CS-induced COPD to elucidate the role of pyruvate kinase M2 (PKM2), a glycolytic enzyme, in CS-induced airway remodeling. Exposure to CS significantly increased PKM2 expression in lung tissues of C57BL/6 mice and BEAS-2B cells, which positively related to the levels of airway inflammation and EMT. Administering PKM2 inhibitor shikonin attenuated CS-induced airway inflammation and EMT process. Moreover, knockdown of PKM2 by small-interfering RNA (siRNA) decreased the release of TNF-α and IL-8, ROS and reversed the CS extract (CSE)-induced changes of N-cadherin and E-cadherin in BEAS-2B cells. In CSE-treated cells, we also observed enhancement of PINK1/Parkin-mediated mitophagy, which were decreased by PKM2 siRNA. Furthermore, pretreatment with mitophagy inducer CCCP before CSE stimulation led to increased expressions of both nuclear and cytosolic PKM2, accompanied by reduction of TGF-β-induced factor homeobox 2 (TGIF2), a repressor of TGF-β1/smad pathway and EMT, while PKM2 knockdown restored the expression of TGIF2. Our results imply that CS induces PKM2 upregulation in airway epithelial cells, acting in synergism with PINK/Parkin-mediated mitophagy, which may initiate and exaggerate airway inflammation and EMT process. Further studies will be required to elucidate more molecular details and other pathways by which PKM2-mitophagy signaling regulates the effector function of airway epithelial.

Nazi, collaborator or opponent? The role of the pathologist Robert Rössle in the Third Reich

For many, Robert Rössle is one of the most important pathologists of the first half of the 20th century. His research in the fields of inflammation, constitution, growth and age, and immunity gave him the status of a pioneer. Because he was not a nominal member of the Nazi Party (NSDAP), Rössle did not have to undergo denazification proceedings and was able to continue his academic career seamlessly after 1945. Only recently, the question of Rössle’s actual role in the Third Reich has been raised – in connection with a possible renaming of the Robert-Rössle-Straße in Berlin. Our paper takes this issue as an opportunity to critically examine Rössle’s involvement in National Socialism. For this study, all available literature and extensive primary material on Rössle from various archives was reviewed and evaluated with regard to the question posed. The investigations show that Rössle held a number of offices in the administrative apparatus of the Nazi state even though not being a party member. They gave him access to high-ranking representatives and most likely also knowledge about medical crimes. Rössle researched and published on hereditary biology and racial hygiene issues, thus supporting the ideology of the Nazi State. Robert Rössle must be regarded as an early proponent of racial hygiene, political collaborator and profiteer of the Third Reich. However, it remains unclear whether he was directly involved in human experiments. There is no evidence that he critically distanced himself from his role in the Third Reich after 1945.

Editorial introductions

Editorial introductions

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

AimThe diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections.MethodsIn September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020.ResultsOverall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication.ConclusionsCurrently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a “common nuclear physicians’ language” throughout all the country.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40336-021-00445-w.

A comparative analysis of NLRP3-related inflammatory mediators in synovial fluid in temporomandibular joint osteoarthritis and internal derangement

BackgroundThe nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathway is a highlighted topic in the field of inflammation. However, there is little research on the relationship between the NLRP3 inflammasome pathway and temporomandibular joint osteoarthritis (TMJOA). The aim of this study was to examine the expression of inflammatory mediators related to the NLRP3 inflammasome in the synovial fluid of patients with condylar cartilage degeneration and verify the clinical effects of sodium hyaluronic acid (HA) treatment on TMJOA.MethodsPatients diagnosed with temporomandibular joint internal derangement (TMJID) without condylar defects and TMJOA with condylar defects were divided into two groups. There were thirty patients in each group, and inflammatory mediators related to the NLRP3 inflammasome, including interleukin-1 beta (IL-1β), IL-18, NLRP3, and cysteinyl aspartate specific proteinase 1 (CASP1), in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Eighteen patients in the TMJOA group were retested after two HA treatments to evaluate the therapeutic effects of HA.ResultsIL-1β, IL-18, NLRP3 and CASP1 were all positive in the two groups, and TMJOA patients with condylar defects had higher expression of these molecules than TMJID patients (P < 0.05). IL-1β, IL-18, and NLRP3 were decreased after two HA treatments (P<0.05), but there was no significant difference in CASP1 after two HA injections (P = 0.549).ConclusionsThe NLRP3 inflammasome signaling pathway may be involved in condylar degeneration. HA could reduce some inflammatory molecules to alleviate inflammation.

Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization

Inflammation plays a crucial role in the occurrence and development of renal fibrosis, which ultimately results in end-stage renal disease (ESRD). There is new focus on lymphangiogenesis in the field of inflammation. Recent studies have revealed the association between lymphangiogenesis and renal fibrosis, but the source of lymphatic endothelial cells (LECs) is not clear. It has also been reported that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms in other tissues. We hypothesized that there was a close relationship between macrophages and lymphatic endothelial progenitor cells in renal fibrosis. In this study, we demonstrated that lymphangiogenesis occurred in a renal fibrosis model and was positively correlated with the degree of fibrosis and macrophage infiltration. Compared to resting (M0) macrophages and alternatively activated (M2) macrophages, classically activated (M1) macrophages predominantly transdifferentiated into LECs in vivo and in vitro. VEGF-C further increased M1 macrophage polarization and transdifferentiation into LECs by activating VEGFR3. It was suggested that VEGF-C/VEGFR3 pathway activation downregulated macrophage autophagy and subsequently regulated macrophage phenotype. The induction of autophagy in macrophages by rapamycin decreased M1 macrophage polarization and differentiation into LECs. These results suggested that M1 macrophages promoted lymphangiogenesis and contributed to newly formed lymphatic vessels in the renal fibrosis microenvironment, and VEGF-C/VEGFR3 signaling promoted macrophage M1 polarization by suppressing macrophage autophagy and then increased the transdifferentiation of M1 macrophages into LECs.

Editorial introductions

Editorial introductions

Generation and Characterization of Inducible Lung and Skin-Specific IL-22 Transgenic Mice.

IL-22 is an IL-10 family cytokine that is increased in asthma and atopic dermatitis (AD). However, the specific role of IL-22 in the pathogenesis of allergic lung inflammation and AD in vivo has yet to be elucidated. We aimed to develop mouse models of allergic diseases in the lung and skin with inducible and tissue-specific expression of IL-22, using a tetracycline (Tet)-controlled system. In this chapter, we describe a series of protocols we have developed to generate a construct that contains the TRE-Tight promoter and mouse IL-22 cDNA based on this system. Furthermore, we describe how to generate TRE-Tight-IL-22 mice through pronuclear microinjection. In our approach, two Tet-on (CC10-rtTA or SPC-rtTA) and a Tet-off (K5-tTA) transgenic mouse lines are selected to crossbreed with TRE-Tight-IL-22 mice to generate inducible tissue-specific transgenic lines. The transgenic strains, CC10-rtTA/TRE-Tight-IL-22 (CC10-rtTA-IL-22) or SPC-rtTA/TRE-Tight-IL-22 (SPC-rtTA-IL-22) mice, do not produce detectable levels of IL-22 in their bronchoalveolar lavage (BAL) samples in the absence of doxycycline (Dox). However, oral Dox treatment of these mice induces IL-22 expression in the BAL, and the airway and lung epithelial cells. For K5-tTA/TRE-Tight-IL-22 (K5-tTA-IL-22) mice, to avoid potential IL-22 toxicity to mouse embryos, Dox is given starting at the time of breeding to suppress tTA and to keep the IL-22 transgene off until the K5-tTA-IL-22 mice are 6weeks old. Experiments are then initiated by withdrawing Dox from the drinking water. In all cases, IL-22 protein can be detected by immunohistochemistry in the skin of Tg(+) animals, but not in the skin of Tg(-) animals. Utilizing transgenic technology based on the Tetracycline-controlled system, we have established inducible transgenic mouse models in which cytokine IL-22 can be expressed specifically in the lung or skin. These models are valuable for studies in vivo in a broad range of diseases involving IL-22 and will provide a new platform for research and for seeking novel therapeutics in the fields of inflammation, asthma, and allergic dermatitis.

The Efficacy of an Energy-Restricted Anti-Inflammatory Diet for the Management of Obesity in Younger Adults.

There is growing evidence of the dietary impact on obesity-induced low-grade chronic inflammation and the associated chronic non-communicable diseases modification. We determined changes in body composition and cardiometabolic and inflammatory status of participants with obesity after 24 weeks of a dietary intervention based on an energy-reduced anti-inflammatory diet and examined the relationship of these changes with changes in the inflammatory potential of the diet. The anthropometric and body composition parameters of 81 participants (average age of 43 years, 74 women) were assessed. Metabolic status was determined using the glycemic and lipid statuses, and the cardiometabolic index and inflammatory status were determined using the concentration of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). The inflammatory potential of the diet was assessed using the Dietary Inflammatory Index (DII®). Intervention with an anti-inflammatory diet resulted in a significant reduction in body weight and visceral adipose tissue and caused improvements in the participants’ cardiometabolic and inflammatory statuses. The anti-inflammatory diet was shown to be effective regarding obesity management. The study data could advance current scientific knowledge in the field of inflammation and diet, provide guidelines for obesity management, and find its application in routine clinical practice.

Evaluation of P2X7 Receptor Function in Tumor Contexts Using rAAV Vector and Nanobodies (AAVnano).

Adenosine triphosphate (ATP) represents a danger signal that accumulates in injured tissues, in inflammatory sites, and in the tumor microenvironment. Extracellular ATP is known to signal through plasma membrane receptors of the P2Y and P2X families. Among the P2X receptors, P2X7 has attracted increasing interest in the field of inflammation as well as in cancer. P2X7 is expressed by immune cells and by most malignant tumor cells where it plays a crucial yet complex role that remains to be clarified. P2X7 activity has been associated with production and release of pro-inflammatory cytokines, modulation of the activity and survival of immune cells, and the stimulation of proliferation and migratory properties of tumor cells. Hence, P2X7 plays an intricate role in the tumor microenvironment combining beneficial and detrimental effects that need to be further investigated. For this, we developed a novel methodology termed AAVnano based on the use of Adeno-associated viral vectors (AAV) encoding nanobodies targeting P2X7. We discuss here the advantages of this tool to study the different functions of P2X7 in cancer and other pathophysiological contexts.