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1.
Front Immunol ; 13: 966917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159799

RESUMO

Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71+ and FasL+) CD8+ T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.


Assuntos
Metapneumovirus , Infecções por Paramyxoviridae , Animais , Linfócitos T CD8-Positivos , Feminino , Humanos , Pulmão , Contagem de Linfócitos , Masculino , Camundongos
2.
Oxid Med Cell Longev ; 2021: 6331630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539970

RESUMO

Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be useful with a dual-directional purpose by substituting/hindering with estrogen and estrogen receptor (ER) complex. Hence, daidzein puts forth shielding effects against a great number of diseases, especially those associated with the control of estrogen, such as breast cancer, diabetes, osteoporosis, and cardiovascular disease. However, daidzein also has other ER-independent biological activities, such as oxidative damage reduction acting as an antioxidant, immune regulator as an anti-inflammatory agent, and apoptosis regulation, directly linked to its potential anticancer effects. In this sense, the present review is aimed at providing a deepen analysis of daidzein pharmacodynamics and its implications in human health, from its best-known effects alleviating postmenopausal symptoms to its potential anticancer and antiaging properties.


Assuntos
Isoflavonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Humanos , Isoflavonas/química , Isoflavonas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Glycine max/química , Glycine max/metabolismo
3.
Immunology ; 158(4): 322-339, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31509246

RESUMO

Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60-70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.


Assuntos
Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Rim/patologia , Lúpus Eritematoso Sistêmico/terapia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Antinucleares/sangue , Diferenciação Celular , Células Cultivadas , Células Dendríticas/transplante , Dexametasona/metabolismo , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos MRL lpr , Pirazinas/metabolismo , Pirróis/metabolismo , Rosiglitazona/metabolismo
4.
Front Immunol ; 8: 1643, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29230219

RESUMO

The mononuclear phagocyte system (MPS) comprises of monocytes, macrophages (MΦ), and dendritic cells (DCs). MPS is part of the first line of immune defense against a wide range of pathogens, including viruses, such as the human respiratory syncytial virus (hRSV). The hRSV is an enveloped virus that belongs to the Pneumoviridae family, Orthopneumovirus genus. This virus is the main etiological agent causing severe acute lower respiratory tract infection, especially in infants, children and the elderly. Human RSV can cause bronchiolitis and pneumonia and it has also been implicated in the development of recurrent wheezing and asthma. Monocytes, MΦ, and DCs significantly contribute to acute inflammation during hRSV-induced bronchiolitis and asthma exacerbation. Furthermore, these cells seem to be an important component for the association between hRSV and reactive airway disease. After hRSV infection, the first cells encountered by the virus are respiratory epithelial cells, alveolar macrophages (AMs), DCs, and monocytes in the airways. Because AMs constitute the predominant cell population at the alveolar space in healthy subjects, these cells work as major innate sentinels for the recognition of pathogens. Although adaptive immunity is crucial for viral clearance, AMs are required for the early immune response against hRSV, promoting viral clearance and controlling immunopathology. Furthermore, exposure to hRSV may affect the phagocytic and microbicidal capacity of monocytes and MΦs against other infectious agents. Finally, different studies have addressed the roles of different DC subsets during infection by hRSV. In this review article, we discuss the role of the lung MPS during hRSV infection and their involvement in the development of bronchiolitis.

6.
Immunol Lett ; 184: 76-83, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28216261

RESUMO

Accumulating evidence suggests a close bidirectional communication and regulation between the neuroendocrine and immune systems. Thyroid hormones (THs) can exert responses in various immune cells, e.g., monocytes, macrophages, natural killer cells, and lymphocytes, affecting several inflammation-related processes (such as, chemotaxis, phagocytosis, reactive oxygen species generation, and cytokines production). The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions, including sepsis, inflammation, autoimmune diseases and viral infections. Under these conditions, TH therapy could contribute to restoring normal physiological functions. Here we discuss the effects of THs and thyroid stimulating hormone (TSH) on the immune system and the contribution to inflammation and pathogen clearance, as well as the consequences of thyroid pathologies over the function of the immune system.


Assuntos
Sistema Imunitário/citologia , Sistema Imunitário/fisiologia , Hormônios Tireóideos/metabolismo , Tireotropina/metabolismo , Animais , Autoimunidade , Interações Hospedeiro-Patógeno/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Inflamação/etiologia , Inflamação/metabolismo , Neuroimunomodulação , Transdução de Sinais , Hormônios Tireóideos/farmacologia , Tireotropina/farmacologia
7.
Virulence ; 8(6): 685-704, 2017 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27911218

RESUMO

Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections. In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.


Assuntos
Metapneumovirus/patogenicidade , Infecções por Paramyxoviridae/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções Respiratórias/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa , Idoso , Animais , Linfócitos B/imunologia , Criança , Citocinas , Humanos , Evasão da Resposta Imune , Lactente , Metapneumovirus/imunologia , Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/virologia , Pneumonia/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/fisiologia , Infecções Respiratórias/virologia , Replicação Viral
8.
Arch Immunol Ther Exp (Warsz) ; 65(2): 123-136, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27585815

RESUMO

Hormonal homeostasis is crucial for keeping a competent and healthy immune function. Several hormones can modulate the function of various immune cells such as dendritic cells (DCs) by influencing the initiation of the immune response and the maintenance of peripheral tolerance to self-antigens. Hormones, such as estrogens, prolactin, progesterone and glucocorticoids may profoundly affect DCs differentiation, maturation and function leading to either a pro-inflammatory or an anti-inflammatory (or tolerogenic) phenotype. If not properly regulated, these processes can contribute to the pathogenesis of autoimmune disease. An unbalanced hormonal status may affect the production of pro-inflammatory cytokines, the expression of activating/inhibitory receptors and co-stimulatory molecules on conventional and plasmacytoid DCs (pDCs), conferring susceptibility to develop autoimmunity. Estrogen receptor (ER)-α signaling in conventional DCs can promote IFN-α and IL-6 production and induce the expression of CD40, CD86 and MHCII molecules. Furthermore, estrogen modulates the pDCs response to Toll-like receptor ligands enhancing T cell priming. During lupus pathogenesis, ER-α deficiency decreased the expression of MHC II on pDCs from the spleen. In contrast, estradiol administration to lupus-prone female mice increased the expression of co-stimulatory molecules, enhanced the immunogenicity and produced large amounts of IL-6, IL-12 and TNF-α by bone marrow-derived DCs. These data suggest that estradiol/ER signaling may play an active role during lupus pathology. Similarly, understanding hormonal modulation of DCs may favor the design of new therapeutic strategies based on autologous tolerogenic DCs transfer, especially in sex-biased systemic autoimmune diseases. In this review, we discuss recent data relative to the role of different hormones (estrogen, prolactin, progesterone and glucocorticoids) in DC function during systemic autoimmune pathogenesis.


Assuntos
Doenças Autoimunes/terapia , Diferenciação Celular , Células Dendríticas/citologia , Hormônios/uso terapêutico , Animais , Fator Ativador de Células B/metabolismo , Modelos Animais de Doenças , Estrogênios/metabolismo , Predisposição Genética para Doença , Glucocorticoides/metabolismo , Humanos , Inflamação , Lúpus Eritematoso Sistêmico/metabolismo , Camundongos , Fenótipo , Progesterona/metabolismo , Prolactina/metabolismo , Receptores de IgG/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo
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