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1.
Medicine (Baltimore) ; 99(39): e22417, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991475

RESUMO

It has become evident that positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (FDG PET-CT) can detect anti-tumor immune response induced by various immunotherapies. To evaluate whether FDG PET-CT could detect anti-cancer immune response caused by cancer vaccine therapy, we performed a retrospective analysis of FDG PET-CT imaging of patients who were treated with Wilms Tumor 1 (WT1) vaccine therapy in Osaka University during July 2008 and June 2018. Increased FDG uptakes were detected in WT1-vaccinated skin and their draining lymph nodes during the repeated vaccination. While the FDG uptakes seemed to decrease with time after the cessation of WT1 peptide vaccinations, persistence of FDG uptakes for years in WT1-vaccinated skin were also observed in 2 cases who showed good clinical course. Moreover, the FDG uptakes of patients treated with the combination vaccine of WT1 specific cytotoxic T cell (CTL) and helper peptides were significantly stronger than of those treated with the WT1 CTL peptide alone. Since it is evident that the combination vaccine can induce a more robust anti-tumor immunity than can CTL peptide vaccine alone, the FDG uptakes in WT1-vaccinated skin might reflect the degree of immune response. These results suggest that PET-CT might be a good tool for prediction of anti-tumor immune response induced by WT1 vaccine therapy. Larger scale prospective studies therefore seem to be warranted.


Assuntos
Vacinas Anticâncer , Fluordesoxiglucose F18/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Pele/diagnóstico por imagem , Proteínas WT1/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/imunologia , Pele/metabolismo
2.
PLoS Pathog ; 16(9): e1008799, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898164

RESUMO

Professional antigen-presenting cells (APCs), like macrophages (Mϕs) and dendritic cells (DCs), are central players in the induction of natural and vaccine-induced immunity to malaria, yet very little is known about the interaction of SPZ with human APCs. Intradermal delivery of whole-sporozoite vaccines reduces their effectivity, possibly due to dermal immunoregulatory effects. Therefore, understanding these interactions could prove pivotal to malaria vaccination. We investigated human APC responses to recombinant circumsporozoite protein (recCSP), SPZ and anti-CSP opsonized SPZ both in monocyte derived MoDCs and MoMϕs. Both MoDCs and MoMϕs readily took up recCSP but did not change phenotype or function upon doing so. SPZ are preferentially phagocytosed by MoMϕs instead of DCs and phagocytosis greatly increased after opsonization. Subsequently MoMϕs show increased surface marker expression of activation markers as well as tolerogenic markers such as Programmed Death-Ligand 1 (PD-L1). Additionally they show reduced motility, produce interleukin 10 and suppressed interferon gamma (IFNγ) production by antigen specific CD8+ T cells. Importantly, we investigated phenotypic responses to SPZ in primary dermal APCs isolated from human skin explants, which respond similarly to their monocyte-derived counterparts. These findings are a first step in enhancing our understanding of pre-erythrocytic natural immunity and the pitfalls of intradermal vaccination-induced immunity.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Macrófagos/imunologia , Malária/imunologia , Plasmodium berghei/imunologia , Proteínas de Protozoários/imunologia , Pele/imunologia , Esporozoítos/imunologia , Animais , Células Cultivadas , Feminino , Humanos , Macrófagos/parasitologia , Malária/parasitologia , Camundongos , Pele/parasitologia
3.
PLoS Negl Trop Dis ; 14(9): e0008601, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886659

RESUMO

Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Sarcoptes scabiei/imunologia , Escabiose/veterinária , Sus scrofa/imunologia , Sus scrofa/parasitologia , Animais , Citocinas/genética , Citocinas/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Imunomodulação/imunologia , Escabiose/imunologia , Escabiose/patologia , Pele/imunologia , Pele/parasitologia , Pele/patologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/parasitologia , Células Th17/imunologia , Células Th2/imunologia , Transcriptoma/genética
4.
PLoS One ; 15(8): e0237705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833973

RESUMO

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This broad influence has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. A key aim of the present study was to examine how PCB exposure at different doses (0, 100, 500, 1000 ppm i.p.) altered wound healing in exercised versus non-exercised subgroups of mice. We examined PCB effects on immune function in more depth by analyzing the concentrations of cytokines, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) in these wounds inflicted by punch biopsy. Mice were euthanized at Day 3 or Day 5 after PCB injection (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Results revealed that wound healing was not signficantly impacted by either PCB exposure or exercise, but there were patterns of delays in healing that depended on PCB dose. Changes in cytokines were also observed and depended on PCB dose and exercise experience. For example, IL-1ß concentrations in Day 5 mice without PCB administration were 33% less in exercised mice than mice not exercised. However, IL-1ß concentrations in Day 3 mice administered 100 ppm were 130% greater in exercised mice than not exercisedmice. Changes in the other measured cytokines varied with mainly depressions at lesser PCB doses and elevations at higher doses. Exercise had diverse effects on cytokine levels, but increased cytokine levels in the two greater doses. Explanations for these diverse effects include the use of young animals with more rapid wound healing rates less affected by toxin exposure, as well as PCB-mediated compensatory effects at specific doses which could actually enhance immune function. Future work should examine these interactions in more detail across a developmental time span. Understanding how manipulating the effects of exposure to environemntal contaminants using behavioral modification could be very useful in certain high risk populations or exposed individuals.


Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Condicionamento Físico Animal/fisiologia , Bifenilos Policlorados/toxicidade , Cicatrização/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Pele/imunologia , Pele/lesões , Pele/metabolismo , Cicatrização/efeitos dos fármacos
5.
Mol Immunol ; 126: 95-100, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32795664

RESUMO

Although T cells are considered as the central component in immune-mediated diseases, supportive evidence has demonstrated that B cells also contribute to the progression of these diseases. B cells are divided into various subsets according to their secreted cytokines. Different B cell subsets play diverse roles in immune-mediated dermatoses. Regulatory B cells (Bregs) are defined functionally by their ability to secrete IL-10, which has been revealed to contribute to immunological tolerance. Drugs that deplete B cells, such as rituximab, are now used for the treatment of several immune-mediated dermatoses. In this review, we present and discuss the current knowledge on the roles of B cells in several immune-mediate dermatoses including psoriasis, pemphigus, bullous pemphigoid, and dermatomyositis, atopic dermatitis.


Assuntos
Linfócitos B Reguladores/imunologia , Dermatite Atópica/imunologia , Dermatomiosite/imunologia , Penfigoide Bolhoso/imunologia , Pênfigo/imunologia , Psoríase/imunologia , Animais , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/metabolismo , Dermatite Atópica/sangue , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Dermatomiosite/sangue , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Desmogleína 3/metabolismo , Modelos Animais de Doenças , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Interleucina-10/metabolismo , Depleção Linfocítica/métodos , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Pênfigo/sangue , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/patologia , Pele/imunologia , Pele/patologia
8.
Proc Natl Acad Sci U S A ; 117(28): 16465-16474, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601220

RESUMO

Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.


Assuntos
Arthrodermataceae/fisiologia , Microbiota , Psoríase/imunologia , Pele/microbiologia , Animais , Arthrodermataceae/classificação , Arthrodermataceae/genética , Arthrodermataceae/isolamento & purificação , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/microbiologia , Feminino , Humanos , Imunidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Psoríase/microbiologia , Psoríase/patologia , Pele/imunologia , Pele/patologia , Simbiose , Células Th17/imunologia
11.
Immunogenetics ; 72(5): 315-323, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32556497

RESUMO

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.


Assuntos
Dermatite Atópica/veterinária , Doenças do Cão/genética , Regulação da Expressão Gênica/imunologia , Pele/imunologia , Animais , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Doenças do Cão/imunologia , Cães , Inflamação/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
12.
Proc Natl Acad Sci U S A ; 117(25): 14365-14375, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513690

RESUMO

Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA), lncFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages. lncFAO is induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chi monocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found that lncFAO directly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO. lncFAO deletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism, lncFAO acts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.


Assuntos
Ácidos Graxos/metabolismo , Inflamação/imunologia , Macrófagos/imunologia , Subunidade beta da Proteína Mitocondrial Trifuncional/genética , RNA Longo não Codificante/metabolismo , Animais , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Masculino , Camundongos , Subunidade beta da Proteína Mitocondrial Trifuncional/metabolismo , Oxirredução , Cultura Primária de Células , RNA Longo não Codificante/genética , Pele/imunologia , Pele/lesões , Cicatrização/imunologia
13.
Proc Natl Acad Sci U S A ; 117(25): 14354-14364, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513697

RESUMO

Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammation-resolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in Alx/Fpr2 have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of Alx/Fpr2, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair.


Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Isquemia/imunologia , Neovascularização Fisiológica/imunologia , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo , Cicatrização/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Humanos , Isquemia/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Cultura Primária de Células , RNA-Seq , Receptores de Formil Peptídeo/genética , Receptores de Lipoxinas/genética , Transdução de Sinais/imunologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/lesões , Pele/patologia , Transcrição Genética/imunologia
14.
Br J Dermatol ; 183(3): 431-442, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32479680

RESUMO

BACKGROUND: The infection caused by the recently identified SARS-CoV-2, called coronavirus disease-19 (COVID-19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID-19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in patients with COVID-19. OBJECTIVES: To provide a brief overview of cutaneous lesions associated with COVID-19. METHODS: A literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding the clinical and histological features of COVID-19-associated skin manifestations. RESULTS: The literature reports showed a great heterogeneity in COVID-19-associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the roles of a hyperactive immune response, complement activation and microvascular injury have been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: (i) urticarial rash; (ii) confluent erythematous-maculopapular-morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain-like acral pattern; (v) livedo reticularis-livedo racemosa-like pattern; and (vi) purpuric 'vasculitic' pattern. These six patterns can be merged into two main groups: the first - inflammatory and exanthematous - includes the first three groups listed above, and the second includes the vasculopathic and vasculitic lesions of the last three groups. CONCLUSIONS: The possible presence of cutaneous findings leading to suspect COVID-19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic values of such cutaneous manifestations.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Dermatopatias/diagnóstico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diagnóstico Diferencial , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Pele/irrigação sanguínea , Pele/imunologia , Pele/patologia , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Dermatopatias/patologia
15.
J Am Acad Dermatol ; 83(3): 870-875, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32502585

RESUMO

BACKGROUND: During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known. OBJECTIVE: To investigate the pathologic features of chilblain-like lesions. METHODS: Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results). RESULTS: Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4+) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels). CONCLUSIONS: Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.


Assuntos
Betacoronavirus/isolamento & purificação , Pérnio/diagnóstico , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Dermatopatias/diagnóstico , Pele/patologia , Adolescente , Adulto , Betacoronavirus/imunologia , Biópsia , Pérnio/imunologia , Pérnio/patologia , Pérnio/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diagnóstico Diferencial , Feminino , Imunofluorescência , França , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pele/imunologia , Pele/virologia , Dermatopatias/imunologia , Dermatopatias/patologia , Dermatopatias/virologia , Dedos do Pé , Adulto Jovem
18.
Cell Immunol ; 354: 104147, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32593012

RESUMO

CARD14 is a scaffold molecule predominantly expressed in keratinocytes and genetic variants in the CARD14 gene confer an increased risk of inflammatory skin disease. Due to its association with common skin diseases psoriasis and atopic dermatitis, the biological function of CARD14 is of relevant interest to human health. CARD14 recruits BCL10 and MALT1 to form the CARD-BCL10-MALT1 complex, which modulates NF-κB and MAPK signalling pathways, yet little is known about how CARD14 is regulated or activated in the context of the innate immune response and in chronic inflammation. This review summarises the current understanding of the molecular function and regulatory mechanisms of CARD14 and highlights recent findings in human disease and murine mouse models.


Assuntos
Inflamação/imunologia , Queratinócitos/metabolismo , Pele/imunologia , Animais , Proteína 10 de Linfoma CCL de Células B/metabolismo , Proteínas Adaptadoras de Sinalização CARD , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Guanilato Quinases , Humanos , Imunidade Inata , Queratinócitos/patologia , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais
19.
Ann Allergy Asthma Immunol ; 125(5): 528-534, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32474160

RESUMO

OBJECTIVE: To explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation. DATA SOURCES: PubMed and Web of Science were searched using the keywords biodiversity, nature relatedness, allergic disease, microbiome, noncommunicable diseases, coronavirus disease 2019, and associated terms. STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity. RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects against allergy and both acute and chronic inflammatory disorders. These important links to ecopsychological constructs of the extinction of experience, which indicates that loss of direct, personal contact with biodiversity (wildlife and the more visible elements of the natural world), might lead to emotional apathy and irresponsible behaviors toward the environment. CONCLUSION: The immune system is a useful early barometer of environmental effects and, by means of the microbiome, is a measure of the way in which our current experiences differ from our ancestral past. Although we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspects of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, and physical activity and promote environmental responsibility.


Assuntos
Alérgenos/imunologia , Infecções por Coronavirus/prevenção & controle , Suscetibilidade a Doenças/imunologia , Hipersensibilidade/prevenção & controle , Microbiota/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Alérgenos/administração & dosagem , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Biodiversidade , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Ecossistema , Exposição Ambiental/análise , Extinção Biológica , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/virologia , Interação Gene-Ambiente , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/microbiologia , Sistema Imunitário/efeitos dos fármacos , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pele/imunologia , Pele/microbiologia , Pele/virologia
20.
Nat Commun ; 11(1): 2858, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504051

RESUMO

Metastatic melanoma is challenging to manage. Although targeted- and immune therapies have extended survival, most patients experience therapy resistance. The adaptability of melanoma cells in nutrient- and therapeutically-challenged environments distinguishes melanoma as an ideal model for investigating therapy resistance. In this review, we discuss the current available repertoire of melanoma models including two- and three-dimensional tissue cultures, organoids, genetically engineered mice and patient-derived xenograft. In particular, we highlight how each system recapitulates different features of melanoma adaptability and can be used to better understand melanoma development, progression and therapy resistance.


Assuntos
Antinematódeos/farmacologia , Modelos Animais de Doenças , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Antinematódeos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Camundongos , Camundongos Transgênicos , Organoides , Pele/citologia , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Esferoides Celulares
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