RESUMO
Thyroid carcinoma is the most common endocrine malignancy and its prevalence has recently been increasing worldwide. We previously reported that the level of sorting nexin 5 (Snx5), an endosomal translocator, is preferentially decreased during the progression of well-differentiated thyroid carcinoma into poorly differentiated carcinoma. To address the functional role of Snx5 in the development and progression of thyroid carcinoma, we established Snx5-deficient (Snx5-/- ) mice. In comparison to wild-type (Snx5+/+ ) mice, Snx5-/- mice showed enlarged thyroid glands that consisted of thyrocytes with large irregular-shaped vacuoles. Snx5-/- thyrocytes exhibited a higher growth potential and higher sensitivity to thyroid-stimulating hormone (TSH). A high content of early endosomes enriched with TSH receptors was found in Snx5-/- thyrocytes, suggesting that loss of Snx5 caused retention of the TSH receptor (TSHR) in response to TSH. Similar data were found for internalized EGF in primary thyrocytes. The increased TSH sensitivities in Snx5-/- thyrocytes were also confirmed by results showing that Snx5-/- mice steadily developed thyroid tumors with high metastatic potential under high TSH. Furthermore, a thyroid cancer model using carcinogen and an anti-thyroidal agent revealed that Snx5-/- mice developed metastasizing thyroid tumors with activation of MAP kinase and AKT pathways, which are postulated to be major pathways of malignant progression of human thyroid carcinoma. Our results suggest that thyrocytes require Snx5 to lessen tumorigenic signaling driven by TSH, which is a major risk factor for thyroid carcinoma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Nexinas de Classificação/genética , Neoplasias da Glândula Tireoide/patologia , Animais , Células Cultivadas , Progressão da Doença , Camundongos Transgênicos , Receptores de Fatores de Crescimento/metabolismo , Transdução de Sinais/fisiologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/metabolismoRESUMO
T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B-cell lymphoma-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(-/-) mice were much higher than those in wild-type (WT) mice. In addition, expansion of Tfh cells within Bob1(-/-) CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(-/-) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3-induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of TCRs.
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Osteosarcoma is a rare but highly malignant tumor occurring most frequently in adolescents. The prognosis of non-responders to chemotherapy is still poor, and new treatment modalities are needed. To develop peptide-based immunotherapy, we previously identified autologous cytotoxic T lymphocyte-defined osteosarcoma antigen papillomavirus binding factor (PBF) in the context of HLA-B55 and the cytotoxic T lymphocyte epitope (PBF A2.2) presented by HLA-A2. PBF and HLA class I are expressed in â¼90 and 70% of various sarcomas, respectively. However, the expression status of peptide PBF A2.2 presented by HLA-A2 on osteosarcoma cells has remained unknown because it is difficult to generate a specific probe that reacts with the HLA·peptide complex. For detection and qualification of the HLA-A*02:01·PBF A2.2 peptide complex on osteosarcoma cells, we tried to isolate a single chain variable fragment (scFv) antibody directed to the HLA-*A0201·PBF A2.2 complex using a naïve scFv phage display library. As a result, scFv clone D12 with high affinity (KD = 1.53 × 10(-9) M) was isolated. D12 could react with PBF A2.2 peptide-pulsed T2 cells and HLA-A2+PBF+ osteosarcoma cell lines and simultaneously demonstrated that the HLA·peptide complex was expressed on osteosarcoma cells. In conclusion, scFv clone D12 might be useful to select candidate patients for PBF A2.2 peptide-based immunotherapy and develop antibody-based immunotherapy.
Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/imunologia , Neoplasias Ósseas/imunologia , Osteossarcoma/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Apresentação de Antígeno , Antígenos de Neoplasias/genética , Sequência de Bases , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Antígeno HLA-A2/genética , Antígeno HLA-A2/imunologia , Antígenos HLA-B/imunologia , Humanos , Imunoterapia Ativa , Dados de Sequência Molecular , Osteossarcoma/genética , Osteossarcoma/terapia , Papillomaviridae/imunologia , Biblioteca de Peptídeos , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Linfócitos T Citotóxicos/imunologiaRESUMO
Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR+Asthma). To determine the pathophysiologic features of AR and AR+Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR+Asthma patients. The results showed polarization of Tfh2 cells within Tfh cell subsets in both AR and AR+Asthma cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR+Asthma cases. Moreover, we found significant correlations of fractional exhaled nitric oxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma.
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Asma/complicações , Linfócitos B Reguladores/fisiologia , Rinite Alérgica/complicações , Linfócitos T Auxiliares-Indutores/classificação , Linfócitos T Auxiliares-Indutores/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The identification of balanomorph larvae plays an important role in ecological study and for protection against biofouling. However, it is difficult to identify species of cyprids (settling larvae) of balanomorph barnacles, as they show remarkably similar morphology. Some authors have suggested distinguishing cyprids of different species by carapace length, pigmentation, and fine carapace detail. However, such criteria are only applicable to a narrow range of balanomorph species. Recently, we were have serendipitously found species-specific distribution of fluorescent substances in cultured cyprids obtained from adult balanomorph barnacles, collected near the coast of Japan. Fluorescent patterns (FPs) of cyprids from 11 species were classified into five major groups. Cyprids specimens collected from the field were estimated, based on the FPs and other morphological characteristics (pigmentation and carapace length), after which their species were identified using the following two criteria: the morphology of adults derived from the field cyprids that adhered to a culture dish, and cyprid 12S rRNA gene sequence. The results of species estimation by FPs largely corresponded to the correct species identification. Other FP groups were found in the field cyprids. This study of FPs should be helpful for identification of cyprid species.
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Fluorescência , Thoracica/classificação , Thoracica/fisiologia , Animais , Larva/classificação , Larva/fisiologia , Filogenia , Especificidade da EspécieRESUMO
Bacterial photosynthetic membrane proteins, light-harvesting antenna complex (LH1), reaction center (RC), and their combined 'core' complex (LH1-RC) are functional elements in the primary photosynthetic events, i.e., capturing and transferring light energy and subsequent charge separation. These photosynthetic units (PSUs) isolated from Rhodospirillum rubrum (Rs. rubrum) were assembled onto an ITO electrode modified with 3-aminopropyltriethoxysilane (APS-ITO). The near IR absorption spectra of PSUs on the assembled electrodes were identical to those of solutions, indicating that the LH1 and LH1-RC core complexes were native on the electrode. Photocurrent response of PSUs on the electrode was examined upon illumination of the LH1 complex at 880 nm. The LH1-RC and a mixed assembly of LH1 and RC exhibited photocurrent response, but not LH1 only, consistent with the function of these PSUs, capturing light energy and transferring electron. This result provides useful methodology for building an artificial fabrication of PSUs on the electrode.
Assuntos
Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Compostos de Estanho/química , Membrana Celular/química , Eletrodos , Complexos de Proteínas Captadores de Luz/química , Complexos de Proteínas Captadores de Luz/isolamento & purificação , Modelos Biológicos , Complexo de Proteínas do Centro de Reação Fotossintética/química , Complexo de Proteínas do Centro de Reação Fotossintética/isolamento & purificação , Propilaminas , Rhodospirillum rubrum/citologia , Rhodospirillum rubrum/metabolismo , Silanos/química , Espectrofotometria InfravermelhoRESUMO
We reported here that polyethylene glycol (PEG)-linked manganese pyrochlorophyllide a (PEG-MnPChlide a) possesses remarkable catalytic activity comparable to horseradish peroxidase (HRP). The PEG-MnPChlide a catalyzed the oxidation decoloration reaction of C.I. Acid Orange 7 by hydrogen peroxide under a mild aqueous condition, pH 8.0 at 25 degrees C. The manganese pyrochlorophyride a methylester (MnPChlide a ME) dissolved in a Triton X-100 micellar solution also exhibited the catalytic activity, indicating the micellar environment plays an important role in the catalytic reaction. The reaction rate was accelerated by addition of imidazole. The catalytic reactions were analyzed by Michaelis-Menten kinetics, revealing that the higher reactivity of catalyst-substrate complex is responsible for the present catalytic reaction system.
Assuntos
Compostos Azo/química , Cloro/química , Corantes/química , Manganês/química , Peróxidos/química , Polietilenoglicóis/química , Benzenossulfonatos , Catálise , Peroxidase do Rábano Silvestre/química , Concentração de Íons de Hidrogênio , Imidazóis/química , Octoxinol/químicaRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often cannot be completely controlled by modern medicine. Since multiple factors are intricately involved in the pathogenesis of AD, wide-ranging research is required for further advancement of AD treatment. Epidermal keratinocytes are the forefront to the external environment and play a pivotal role in the initiation of immune reaction against exogenous invasion. OBJECTIVE: Thymic stromal lymphopoietin (TSLP) is a keratinocyte-derived cytokine that induces differentiation and activation of type 2 helper T cells and innate lymphoid cells, cardinal effectors in pathophysiology of AD. We previously reported that ΔNp63, a p53-related molecule, regulates the expression of TSLP receptors and suggested the entity of a potential TSLP autocrine loop in the AD epidermis. In this study, we further explored the significance of p53 family transcription factors in TSLP production from human keratinocytes. METHOD: Expression profile of p73, a p53-related molecule, was evaluated in human AD tissue by immunohistochemistry. In addition, the function of p73 in producing TSLP was investigated with in vitro cultured keratinocytes via molecular biological analysis. RESULTS: ΔNp73 was abundantly expressed in the AD epidermis and increased the release of TSLP via NF-κB activation. Furthermore, the Toll-like receptor 3 signal enhanced ΔNp73 expression and thereby induced TSLP expression. CONCLUSION: Our results indicate that ΔNp73 is an additional participant in the mechanism of TSLP production. Amending the aberrant state of keratinocytes, represented by overexpression of ΔNp73, can be a novel therapeutic target of AD.
Assuntos
Citocinas/metabolismo , Dermatite Atópica/patologia , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Proteína Tumoral p73/metabolismo , Adolescente , Adulto , Idoso , Células Cultivadas , Dermatite Atópica/imunologia , Células Epidérmicas , Epiderme/metabolismo , Feminino , Humanos , Imunidade Inata , Queratinócitos/imunologia , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo , Proteína Tumoral p73/imunologia , Linfopoietina do Estroma do TimoRESUMO
Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH. When we analyzed tonsils of OSA and recurrent tonsillitis (RT) as a control, tonsils of OSA were found to harbor Tfh cells with a nearly 3-fold higher ratio in total CD4+ T cells than that in tonsils of RT. Further analysis showed that, in comparison to Tfh cells of RT tonsils, Tfh cells of OSA tonsils were relatively tolerant to CD3-mediated activation-induced cell death (AICD) and also expressed lower levels of a Bob1 transcription coactivator and IL-4, which fosters the development of GC-B cells. Given that Bob1 controls the proliferative activity in response to CD3 stimulation and has been suggested to have a role in the production of IL-4 in Tfh cells, the unique structure of FRFH is possibly associated with the function of Bob1lo Tfh cells.
Assuntos
Centro Germinativo/patologia , Linfoma Folicular/diagnóstico , Tonsila Palatina/patologia , Linfócitos T Auxiliares-Indutores/fisiologia , Transativadores/metabolismo , Animais , Citotoxicidade Celular Dependente de Anticorpos , Células Cultivadas , Diagnóstico Diferencial , Hiperplasia , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Apneia Obstrutiva do Sono , Transativadores/genéticaRESUMO
Recently, the prevalence of allergic rhinitis has been dramatically increasing worldwide. As conventional therapies for allergic rhinitis, such as antihistamines, leukotriene receptor antagonists, nasal sprays and allergen immunotherapy, have limitations, the development of new drugs is required. Recent studies have revealed that epithelial cell-derived cytokines, including thymic stromal lymphopoietin, interleukin (IL)-25 and IL-33, are able to control immune cells, such as dendritic cells and T cells, thereby acting as 'master switches' in allergic disease. In addition, new roles have been identified for follicular helper T cells and regulatory B cells in allergic disease, and they are considered to be promising targets for new therapies. Thus, crosstalk between epithelial and immune cells, the epimmunome, underlies the pathogenesis of allergic rhinitis. Greater understanding of the epimmunome may lead to breakthroughs in the development of new treatments for allergic rhinitis and will help us cure many patients suffering from its severe symptoms in the future.
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Citocinas/metabolismo , Imunidade Celular/imunologia , Mucosa Nasal/imunologia , Rinite Alérgica/imunologia , Linfócitos T/imunologia , Humanos , Mucosa Nasal/metabolismo , Rinite Alérgica/metabolismoRESUMO
The tonsils are located at the entrance of the pharynx as a cardinal constituent of Waldeyer's ring, taking part not only in local immune responses, but also in systemic immunity. Functional deficits of tonsils primarily underlie the pathogenesis of various characteristic disorders, including tonsillar focal infections such as palmoplantar pustulosis and IgA nephropathy, in addition to the highly prevalent sleep disorder called obstructive sleep apnea syndrome. Although the mechanisms underlying these disorders remain unknown, the tonsils have long been postulated as a unique and enigmatic immune organ. Lymphoid cells and tissues from surgically resected tonsils are often employed to analyze the human immune response from a retrospective view. This approach has provided much new fundamental evidence for understanding innate and acquired immune responses, thereby facilitating further studies in the fields of mucosal immunity and specific humoral immunity originating in the germinal center. Future studies of the tonsils in basic and clinical research are expected to reveal the mechanisms of tonsil-related disorders as well as the nature of human immunity. In this review, which is primarily based on our original research over the past 3 decades, we summarize our findings and discuss the future prospects of studies focusing on the tonsils.
Assuntos
Imunidade nas Mucosas , Tonsila Palatina/imunologia , Mucosa Respiratória/imunologia , HumanosRESUMO
Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs) by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema.
Assuntos
Células Endoteliais/metabolismo , Células Endoteliais/patologia , Homeostase , Leptina/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Interleucina-6/genética , Leptina/farmacologia , Pessoa de Meia-Idade , Proteína 3 Supressora da Sinalização de Citocinas/metabolismoRESUMO
Inflammasomes, large protein complexes typically consisting of a Nod-like receptor (NLR), adapter protein apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1, are postulated to be activated in response to danger signals arising from tumors. Inflammasomes are thought to have critical but contrasting roles through facilitating antitumor immunity and inducing oncogenic factors. However, the role and function of inflammasomes in oropharyngeal carcinoma remain unclear. We analyzed nine specimens of oropharyngeal squamous cell carcinoma (SCC) and determined the expression of NLRP3, ASC, interleukin (IL)-1ß, IL-18 and caspase-1 in the specimens with and without human papilloma virus (HPV) infection using immunohistochemistry, and analyzed the correlations between the altered expression of these proteins and clinicopathological factors of oropharyngeal SCC. We found strong expression of NLRP3, ASC, IL-1ß, IL-18 and caspase-1 in human oropharyngeal SCC and weak or no expression of these proteins in normal tonsils. Furthermore, the distribution of mindbomb E3 ubiquitin protein ligase 1 and inflammasome-associated proteins in oropharyngeal SCC was not significantly different; there was no correlation between the expression of inflammasome-associated proteins and HPV infection. These findings suggest that inflammasomes in oropharyngeal SCC play a key role through facilitating antitumor immunity and the possibility of new roles for inflammasomes in the oropharynx.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Imunidade Inata , Inflamassomos/biossíntese , Neoplasias Orofaríngeas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Feminino , Humanos , Imuno-Histoquímica , Inflamassomos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/imunologiaRESUMO
Defensins are small antimicrobial peptides and effector components of innate immune responses. Recent studies have shed light on their beneficial functions for the prevention of infection and potential for development of new drugs. Here, we showed the expression profiles of human defensins in palatine tonsils with 3 different diseases: tonsillar hypertrophy, recurrent tonsillitis and focal infection of the tonsil. RT-PCR analysis and immunofluorescence revealed that the expression of human α-defensin 4 and ß-defensin 3 (ß3) in palatine tonsils with tonsillar hypertrophy was lower than that in recurrent tonsillitis and focal infection of the tonsil, suggesting that chronic inflammation induces defensin expression. Interestingly, ß2 and ß3 mRNAs were specifically expressed by palatine tonsil tissues but not in human peripheral blood mononuclear cells and mucosa of the small intestine. Additionally, we observed that exposure to a Toll-like receptor 4 ligand, lipopolysaccharide, which is used as a bacterial infection model, increases the production of ß2 in culture supernatants from tonsillar epithelial cells in a dose-dependent manner. Taken together, these results indicate that ß2 produced by tonsillar epithelial cells plays an important role in the innate immune response for bacterial infections.
Assuntos
Defensinas/genética , Regulação da Expressão Gênica , Imunidade Inata/imunologia , Tonsila Palatina/metabolismo , RNA/genética , Tonsilite/genética , Adulto , Células Cultivadas , Defensinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Microscopia de Fluorescência , Tonsila Palatina/diagnóstico por imagem , Tonsila Palatina/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Tonsilite/imunologia , Tonsilite/metabolismo , Adulto JovemRESUMO
It is necessary for the surgeon to be familiar with frontal recess anatomy during an endoscopic approach to the frontal sinuses. The aim of this study was to evaluate the prevalence of frontal recess cells in Japanese adults as well as the association between the frontal recess and the location of the anterior ethmoidal artery (AEA). The frontal recess cells and the AEAs were retrospectively evaluated in CT scans of the nasal and paranasal sinuses for 89 patients. The prevalence of agger nasi cells was 90.7%. The frequency of frontal cell types 1, 2, 3 and 4 was 28.8, 0.6, 2.6 and 0%, respectively. Suprabullar cells (SBCs) and frontal bullar cells (FBCs) were identified in 78/96 sides (81.3%) and 24/96 sides (24%), respectively. The prevalence of the medial group of frontal recess cells (interfrontal sinus septal cells) was 12.4%. In 42/61 sides (68.9%), the AEAs were located within the posterior margin of the SBCs or the FBCs. Therefore, SBCs, FBCs and the vertical portion of the middle turbinate are reliable landmarks for the identification of AEAs.
Assuntos
Artérias/anatomia & histologia , Seio Etmoidal/irrigação sanguínea , Seio Frontal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Conchas Nasais/irrigação sanguínea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Seio Etmoidal/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Conchas Nasais/diagnóstico por imagem , Adulto JovemRESUMO
High-dose chemotherapy may kill not only tumor cells but also immunocytes, and frequently induces severe lymphocytopenia. On the other hand, patients who recover from the nadir maintain immunity against infection, suggesting the existence of an unknown memory T-cell population with stress resistance, long-living capacity, proliferation and differentiation. Recently, the differentiation system of T-cell memory has been clarified using mouse models. However, the human T-cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. Here we report a novel human T-cell memory population, "young memory" T (TYM) cells. TYM cells are defined by positive expression of CD73, which represents high aldehyde dehydrogenase 1 (ALDH1) activity and CXCR3 among CD8(+)CD45RA(+)CD62L(+) T cells. TYM proliferate upon TCR stimulation, with differentiation capacity into TCM and TEM and drug resistance. Moreover, TYM are involved in memory function for viral and tumor-associated antigens in healthy donors and cancer patients, respectively. Regulation of TYM might be very attractive for peptide vaccination, adoptive cell-transfer therapy and hematopoietic stem cell transplantation.
RESUMO
The marine colonial hydroid Tubularia mesembryanthemum produces a morphologically unique dispersive stage, the actinula larva. Detailed observations were made on the behaviors and nematocyte dynamics of actinula larvae during attachment and morphogenesis by employing microscopic and time lapse video techniques. These observations produced four primary results. (1) Actinula larvae demonstrated two forms of attachment: temporary attachment by atrichous isorhiza (AI)-nematocysts discharged from the aboral tentacle (AT) tips-and permanent settlement by cement secretion from the columnar gland cells of the basal protrusion. (2) During larval settlement, numerous AIs were discharged from the AT tips with sinuous movement and rubbing of the tentacles onto the substrata, leading to "nematocyte-printing" around the settlement site. (3) Simultaneous with the discharge of the AIs, migration of stenoteles, desmonemes, and microbasic mastigophores occurred, resulting in a dramatic change of nematocyte composition in the ATs after larval settlement. This was in parallel with changes in larval behavior and the tentacle function. (4) Nematocyte-printing behavior during settlement could be recognized as metamorphic behavior responsible for irreversible changes in AT function, from attachment to feeding and defense.
Assuntos
Comportamento Animal , Meio Ambiente , Hidrozoários/anatomia & histologia , Hidrozoários/crescimento & desenvolvimento , Análise de Variância , Animais , Japão , Larva/fisiologia , Larva/ultraestrutura , Microscopia Eletrônica de Varredura , Morfogênese , Estações do AnoRESUMO
In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and in vitro studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63(lo/-)). Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3). Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63(lo/-) keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3.
Assuntos
Citocinas/imunologia , Dermatite Atópica/imunologia , Pele/imunologia , Receptor 3 Toll-Like/imunologia , Fatores de Transcrição/imunologia , Proteínas Supressoras de Tumor/imunologia , Linhagem Celular , Células Cultivadas , Dermatite Atópica/patologia , Humanos , Queratinócitos/imunologia , Queratinócitos/patologia , Transdução de Sinais , Pele/patologia , Linfopoietina do Estroma do TimoRESUMO
The two-dimensional molecular assembly was accomplished of bacteriochlorophyll a (BChl a) and zinc-substituted BChl a (Zn-BChl a) together with synthetic poly(ethylene glycol)(PEG)-linked light-harvesting (LH) model polypeptides on a gold Au(111) electrode modified with supported lipid bilayers. Model polypeptides for LH1-α from Rhodospirillum (Rs.) rubrum were successfully synthesized and stably assembled with Zn-BChl a in 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1'-glycerol)] (DOPG) lipid bilayers on an electrode at room temperature, as well as in liposomal solution, in which the Zn-BChl a complex unlike BChl a, was stably assembled. The PEG moiety of the model polypeptide assisted the stable assembly with an α-helical conformation of the LH1-α model peptides together with these pigments onto the gold electrode with defined orientation. The photocurrent response depended on the combinations of the pigments and synthetic LH model polypeptides. The results presented herein will be useful for the self-assembly of these complexes on electrodes to construct efficient energy-transfer and electron-transfer reactions between individual pigments in lipid bilayers.