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1.
Eur J Med Chem ; 185: 111842, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31727470

RESUMO

Aryl Hydrocarbon Receptor (AhR) constitutes a major network hub of genomic and non-genomic signaling pathways, connecting host's immune cells to environmental factors. It shapes innate and adaptive immune processes to environmental stimuli with species-, cell- and tissue-type dependent specificity. Although an ever increasing number of studies has thrust AhR into the limelight as attractive target for the development of next-generation immunotherapies, concerns exist on potential safety issues associated with small molecule modulation of the receptor. Selective AhR modulators (SAhRMs) and rapidly metabolized AhR ligands (RMAhRLs) are two classes of receptor agonists that are emerging as interesting lead compounds to bypass AhR-related toxicity in favor of therapeutic effects. In this article, we discuss SAhRMs and RMAhRLs reported in literature, covering concepts underlying their definitions, specific binding modes, structure-activity relationships and AhR-mediated functions.


Assuntos
Doenças do Sistema Imunitário/terapia , Imunoterapia , Receptores de Hidrocarboneto Arílico/agonistas , Animais , Humanos , Doenças do Sistema Imunitário/imunologia , Ligantes , Estrutura Molecular
3.
EBioMedicine ; 44: 716-729, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31201141

RESUMO

The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.


Assuntos
Infecções por Clostridium/microbiologia , Infecções por Clostridium/terapia , Clostridium difficile/fisiologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Animais , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Humanos , Doenças do Sistema Imunitário/etiologia , Doenças do Sistema Imunitário/terapia , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Doenças Metabólicas/etiologia , Doenças Metabólicas/terapia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia
4.
Endocr J ; 66(7): 581-586, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31243183

RESUMO

Immune checkpoint inhibitors (ICIs) have become a promising treatment for advanced malignancies. However, these drugs can induce immune-related adverse events (irAEs) in several organs, including skin, gastrointestinal tract, liver, muscle, nerve, and endocrine organs. Endocrine irAEs comprise hypopituitarism, primary adrenal insufficiency, thyroid dysfunction, hypoparathyroidism, and type 1 diabetes mellitus. These conditions have the potential to lead to life-threatening consequences, such as adrenal crisis, thyroid storm, severe hypocalcemia, and diabetic ketoacidosis. It is therefore important that both endocrinologists and oncologists understand the clinical features of each endocrine irAE to manage them appropriately. This opinion paper provides the guidelines of the Japan Endocrine Society and in part the Japan Diabetes Society for the management of endocrine irAEs induced by ICIs.


Assuntos
Doenças do Sistema Endócrino/induzido quimicamente , Doenças do Sistema Endócrino/terapia , Doenças do Sistema Imunitário/induzido quimicamente , Doenças do Sistema Imunitário/terapia , Fatores Imunológicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Doenças das Glândulas Suprarrenais/induzido quimicamente , Doenças das Glândulas Suprarrenais/terapia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/imunologia , Diabetes Mellitus/terapia , Doenças do Sistema Endócrino/diagnóstico , Humanos , Doenças do Sistema Imunitário/diagnóstico , Fatores Imunológicos/uso terapêutico , Japão , Doenças das Paratireoides/induzido quimicamente , Doenças das Paratireoides/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/terapia
5.
Int J Mol Sci ; 20(9)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31052382

RESUMO

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.


Assuntos
Células Dendríticas/imunologia , Doenças do Sistema Imunitário/imunologia , Células Th2/imunologia , Animais , Humanos , Doenças do Sistema Imunitário/terapia , Imunoterapia/métodos
6.
Scand J Immunol ; 89(6): e12759, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30793341

RESUMO

DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8+ T-cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary.


Assuntos
Afinidade de Anticorpos/imunologia , Linfócitos B/imunologia , Fatores de Troca do Nucleotídeo Guanina/deficiência , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Receptores de Antígenos de Linfócitos B/imunologia , Adolescente , Anticorpos Antibacterianos/imunologia , Linfócitos T CD8-Positivos/imunologia , Pré-Escolar , Clostridium tetani/imunologia , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Haemophilus influenzae tipo b/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Cadeias Pesadas de Imunoglobulinas/genética , Imunoglobulina M/sangue , Memória Imunológica/imunologia , Masculino , Receptores de Antígenos de Linfócitos B/genética
9.
Ann Hematol ; 98(5): 1177-1184, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30610278

RESUMO

Immunoparesis is defined as a reduction in the levels of one, two, or three uninvolved immunoglobulins. However, there are very limited data on the incidence and prognostic significance of immunoparesis recovery 1 year after autologous stem cell transplantation (ASCT) in MM. We reviewed medical records of de novo MM patients who received ASCT at Beijing Chao Yang hospital. One hundred eight MM patients were included in the study. Conventional chemotherapy was administered as induction regimen in 16 patients (14.8%), whereas novel agents were used in 92 patients (85.2%). Most patients had immunoparesis at diagnosis (89.1%) and at the moment of ASCT as well (75%). After a median follow-up of 49 months, in the group with immunoglobulin recovery 1 year after ASCT, there was a trend towards longer progression-free survival (PFS) than in the group with immunoparesis (P = 0.054). And overall survival (OS) was significantly longer in patients with immunoparesis recovery (P = 0.004). In multivariate analysis, immunoparesis recovery 1 year after ASCT was independently associated with improved OS (P = 0.016). In conclusion, lack of immunoparesis recovery 1 year after ASCT in MM patients is associated with significantly shorter OS and this group of patients needs new treatment strategy to improve the prognosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Imunitário , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Doenças do Sistema Imunitário/etiologia , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Taxa de Sobrevida
10.
Blood ; 133(7): 697-709, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30463995

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy is a new pillar in cancer therapeutics; however, its application is limited by the associated toxicities. These include cytokine release syndrome (CRS) and neurotoxicity. Although the IL-6R antagonist tocilizumab is approved for treatment of CRS, there is no approved treatment of neurotoxicity associated with CD19-targeted CAR-T (CART19) cell therapy. Recent data suggest that monocytes and macrophages contribute to the development of CRS and neurotoxicity after CAR-T cell therapy. Therefore, we investigated neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential strategy to manage CART19 cell-associated toxicities. In this study, we show that GM-CSF neutralization with lenzilumab does not inhibit CART19 cell function in vitro or in vivo. Moreover, CART19 cell proliferation was enhanced and durable control of leukemic disease was maintained better in patient-derived xenografts after GM-CSF neutralization with lenzilumab. In a patient acute lymphoblastic leukemia xenograft model of CRS and neuroinflammation (NI), GM-CSF neutralization resulted in a reduction of myeloid and T cell infiltration in the central nervous system and a significant reduction in NI and prevention of CRS. Finally, we generated GM-CSF-deficient CART19 cells through CRISPR/Cas9 disruption of GM-CSF during CAR-T cell manufacturing. These GM-CSFk/o CAR-T cells maintained normal functions and had enhanced antitumor activity in vivo, as well as improved overall survival, compared with CART19 cells. Together, these studies illuminate a novel approach to abrogate NI and CRS through GM-CSF neutralization, which may potentially enhance CAR-T cell function. Phase 2 studies with lenzilumab in combination with CART19 cell therapy are planned.


Assuntos
Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Doenças do Sistema Imunitário/terapia , Inflamação/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Animais , Anticorpos Neutralizantes/farmacologia , Proliferação de Células , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Síndrome , Transplante Heterólogo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Nat Rev Genet ; 20(2): 109-127, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30479381

RESUMO

Biomarker discovery and validation are necessary for improving the prediction of clinical outcomes and patient monitoring. Despite considerable interest in biomarker discovery and development, improvements in the range and quality of biomarkers are still needed. The main challenge is how to integrate preclinical data to obtain a reliable biomarker that can be measured with acceptable costs in routine clinical practice. Epigenetic alterations are already being incorporated as valuable candidates in the biomarker field. Furthermore, their reversible nature offers a promising opportunity to ameliorate disease symptoms by using epigenetic-based therapy. Thus, beyond helping to understand disease biology, clinical epigenetics is being incorporated into patient management in oncology, as well as being explored for clinical applicability for other human pathologies such as neurological and infectious diseases and immune system disorders.


Assuntos
Epigênese Genética , Epigenômica , Doenças do Sistema Imunitário , Doenças do Sistema Nervoso , Medicina de Precisão/métodos , Pesquisa Biomédica/métodos , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/metabolismo , Doenças do Sistema Imunitário/terapia , /metabolismo , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/terapia
12.
Arch Pharm Res ; 42(4): 293-304, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30426387

RESUMO

Immunological disorders such as allergy, autoimmune diseases, auto-inflammatory syndromes and immunological deficiency syndromes are difficult to treat with chemical drugs. Recently, many monoclonal antibodies targeting various molecules including interleukin, tumor necrosis factor-α, cluster of differentiation, integrins, complement C5 and B lymphocyte stimulator are clinically available and give a hope to patients suffering from these intractable diseases. Here, we selected twenty-seven monoclonal antibodies approved by US FDA since 1997 and they are classified according to their target molecules. Although these biomedicines possessed some restrictions such as high cost and susceptible to infectious disease, these drawbacks can be overcome through cost-cutting innovations including biosimilars and careful monitoring. New targets are emerging rapidly and more effective biomedicines with acceptable side effects are in the pipeline for next decade.


Assuntos
Anticorpos Monoclonais/imunologia , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Humanos
13.
Adv Exp Med Biol ; 1201: 93-108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31898783

RESUMO

Mesenchymal stem cells (MSCs) are multipotent cells that can self-renew and differentiate into cells of all germ layers. MSCs can be easily attracted to the site of tissue insult with high levels of inflammatory mediators. The general ability of MSCs to migrate at the sites of tissue injury suggested an innate ability for these cells to be involved in baseline tissue repair. The bone marrow is one of the primary sources of MSCs, though they can be ubiquitous. An attractive property of MSCs for clinical application is their ability to cross allogeneic barrier. However, alone, MSCs are not immune suppressive cells. Rather, they can be licensed by the tissue microenvironment to become immune suppressor cells. Immune suppressor functions of MSCs include those that blunt cytotoxicity of natural killer cells, suppression of T-cell proliferation, and "veto" function. MSCs, as third-party cells, suppress the immune response that generally recapitulates graft-versus-host disease (GvHD) responses. Based on the plastic functions of MSCs, these cells have dominated the field of cell-based therapies, such as anti-inflammatory and drug delivery. Here, we focus on the potential use of MSC for immunological disorders such as Crohn's disease and GvHD.


Assuntos
Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doença de Crohn/imunologia , Doença de Crohn/terapia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Doenças do Sistema Imunitário/patologia , Células Matadoras Naturais/imunologia , Células-Tronco Mesenquimais/citologia
14.
Clin Immunol ; 197: 219-223, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30368009

RESUMO

Early onset multisystem autoimmunity is commonly the defining feature of IPEX. Recurrent sinopulmonary infections and CVID-like phenotype were not previously recognized as a presentation in IPEX. Herein, we describe three extended family members with IPEX. In addition to autoimmunity, all three had a CVID-like presentation consisting of recurrent sinopulmonary infections, hypogammaglobulinemia and B-cell class switching defect. In vitro studies have shown that the B cell class switching defect is not B cell intrinsic. Additionally, a marked increase in circulating T follicular helper (cTFH) cells with high IFN-γ and IL-17 secretion on stimulation was noted in our patients. The dysregulated cTFH cells could contribute to a decreased B cell class switching. However, the exact mechanism of how expanded and dysregulated cTFH lead to B cell class switching defect and hypogammaglobulinemia in our patients is not clear. Our study could extend the clinical spectrum of IPEX to include a CVID-like presentation.


Assuntos
Agamaglobulinemia/imunologia , Autoimunidade/imunologia , Linfócitos B/imunologia , Diabetes Mellitus Tipo 1/congênito , Diarreia/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças do Sistema Imunitário/congênito , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Agamaglobulinemia/terapia , Anemia Hemolítica Autoimune/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/terapia , Eczema/imunologia , Família , Feminino , Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Heterozigoto , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Switching de Imunoglobulina/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Enteropatias/imunologia , Masculino , Pessoa de Meia-Idade , Linhagem , Pneumonia/imunologia , Recidiva , Sinusite/imunologia , Adulto Jovem
16.
Sci Rep ; 8(1): 13535, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201960

RESUMO

Multipotential stromal cells (MSCs) demonstrate strong immunomodulation capabilities following culture expansion. We have previously demonstrated that human cancellous bone fragments (CBFs) clinically used as viable allografts for spinal fusion have resident MSCs that exhibit T cell immunomodulation after monolayer expansion. This study investigated the immunomodulatory ability of these CBFs without MSC culture-expansion. CD4 positive T cells were induced to proliferate using CD3/CD28 stimulation and added to CBFs at different ratios of T cells per gram of CBF. A dose-dependent suppressive effect on T cell proliferation was evident and correlated with increased culture supernatant levels of TGF-ß1, but not PGE2. CBF-driven immunosuppression was reduced in co-cultures with TGF-ß neutralising antibodies and was higher in cell contact compared to non-contact cultures. CBF gene expression profile identified vascular cell adhesion molecule-1, bone marrow stromal antigen 2/CD317 and other interferon signalling pathway members as potential immunomodulatory mediators. The CD317 molecule was detected on the surface of CBF-resident cells confirming the gene expression data. Taken together, these data demonstrate that human clinically used CBFs are inherently immunomodulatory and suggest that these viable allografts may be used to deliver therapeutic immunomodulation for immune-related diseases.


Assuntos
Aloenxertos/imunologia , Matriz Óssea/imunologia , Linfócitos T CD4-Positivos/imunologia , Osso Esponjoso/imunologia , Imunossupressão/métodos , Aloenxertos/metabolismo , Aloenxertos/transplante , Antígenos CD/imunologia , Antígenos CD/metabolismo , Matriz Óssea/metabolismo , Matriz Óssea/transplante , Osso Esponjoso/metabolismo , Osso Esponjoso/transplante , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura/métodos , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Perfilação da Expressão Gênica , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Ativação Linfocitária , Cultura Primária de Células/métodos , Fusão Vertebral/métodos , Transplante Homólogo/métodos , Molécula 1 de Adesão de Célula Vascular/imunologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
17.
Rev Alerg Mex ; 65(3): 217-221, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30176199

RESUMO

The Global Alliance against Chronic Respiratory Diseases (GARD) is a network of organizations coordinated by the World Health Organization. It is a voluntary alliance of national and international organizations, institutions and agencies with global scope that are committed with actions to improve access to prevention, care and essential medications. On its last annual meeting, celebrated in Brussels (Belgium) in September 2017, the need for actions and representation to be grouped by geographic regions was discussed. There are several successful programs regarding morbidity and mortality control of these diseases, and others that improve cost-benefit and quality of life. Thus, SLaai proposes to contribute to the diffusion and knowledge of chronic respiratory diseases magnitude and risk factors, to identify successful programs in Latin America in order for them to be replicated in the region and to generate strategic alliances for the strengthening of joint actions.


Assuntos
Asma/terapia , Hipersensibilidade/terapia , Doenças do Sistema Imunitário/terapia , Agências Internacionais , Transtornos Respiratórios/terapia , Doença Crônica , Congressos como Assunto , Humanos , América Latina
19.
Front Immunol ; 9: 2056, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30254638

RESUMO

Background: One of the greatest challenges for medicine is to find a safe and effective treatment for immune-related diseases. However, due to the low efficacy of the treatment available and the occurrence of serious adverse effects, many groups are currently searching for alternatives to the traditional therapy. In this regard, the use of human mesenchymal stem cells (hMSCs) represents a great promise for the treatment of a variety of immune-related diseases due to their potent immunomodulatory properties. The main objective of this study is, therefore, to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of the administration of hMSCs for the treatment of immune-related diseases was evaluated. Methods: The article search was conducted in PubMed/MEDLINE, Scopus and Web of Science databases. Original research articles assessing the therapeutic potential of hMSCs administration for the in vivo treatment immune-related diseases, published from 1984 to December 2017, were selected and evaluated. Results: A total of 132 manuscripts formed the basis of this systematic review. Most of the studies analyzed reported positive results after hMSCs administration. Clinical effects commonly observed include an increase in the survival rates and a reduction in the severity and incidence of the immune-related diseases studied. In addition, hMSCs administration resulted in an inhibition in the proliferation and activation of CD19+ B cells, CD4+ Th1 and Th17 cells, CD8+ T cells, NK cells, macrophages, monocytes, and neutrophils. The clonal expansion of both Bregs and Tregs cells, however, was stimulated. Administration of hMSCs also resulted in a reduction in the levels of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-1, IL-2, IL-12, and IL-17 and in an increase in the levels of immunoregulatory cytokines such as IL-4, IL-10, and IL-13. Conclusions: The results obtained in this study open new avenues for the treatment of immune-related diseases through the administration of hMSCs and emphasize the importance of the conduction of further studies in this area.


Assuntos
Citocinas/imunologia , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Leucócitos Mononucleares/imunologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Humanos , Doenças do Sistema Imunitário/patologia , Leucócitos Mononucleares/patologia , Células-Tronco Mesenquimais/patologia
20.
Med Hypotheses ; 117: 7-15, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30077201

RESUMO

All traumas suppress the immune system, resulting in higher morbidity and mortality. Infections, poor nutritional status, chronic illness, fatigue, therapies or procedures performed during and after transport also negatively affect the immune system. Large populations are impacted by trauma worldwide and suffer enormous costs in both direct and indirect expenditures from physical, psychological and functional losses. Most therapies and studies of trauma, brain trauma, stroke, immune suppression and their co-morbidities do not address nor discuss methods that promote immune system resuscitation or efficacy to support its role in post-trauma healing and rehabilitation. These omissions present an opportunity for using autologous stored naïve (unexposed to the current trauma and co-morbidities) white blood cell infusions (autologous white blood cell infusion) (AWBCI) to supplement treatment of most traumas, trauma-associated infections, other co-morbidities and immune suppression derived problems in order to improve the global standard of trauma care. We hypothesize to give the traumatized patients back their own immune system that has been 'stored' in some fashion, either cryogenically or just after or during the trauma event [surgery, etc for example]. We emphasize that other treatments should not be replaced - rather we suggest AWBCI as concurrent therapy. We present focused select animal and human studies as proofs of concept to arrive at and support our therapeutic suggestion and hypotheses, flowing historically from donor white blood cell therapy [DLI] to close cohort white blood cell therapy to autologous white blood cell infusion [AWBCI]. We integrate the concept of personalized medicine from an evidence-based framework while maintaining scientific rigor and statistical proof as a basis of our hypotheses.


Assuntos
Lesões Encefálicas/terapia , Doenças do Sistema Imunitário/terapia , Leucócitos/citologia , Acidente Vascular Cerebral/terapia , Ferimentos e Lesões/terapia , Animais , Lesões Encefálicas/complicações , Lesões Encefálicas/imunologia , Comorbidade , Humanos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/imunologia , Camundongos , Modelos Teóricos , Transtornos de Estresse Pós-Traumáticos/imunologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/imunologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/imunologia
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