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111.
Mucosal tissues in the human female reproductive tract (FRT) are primary sites for both gynecological cancers and infections by a spectrum of sexually transmitted pathogens, including human immunodeficiency virus (HIV), that compromise women''s health. While the regulation of innate and adaptive immune protection in the FRT by hormonal cyclic changes across the menstrual cycle and pregnancy are being intensely studied, little to nothing is known about the alterations in mucosal immune protection that occur throughout the FRT as women age following menopause. The immune system in the FRT has two key functions: defense against pathogens and reproduction. After menopause, natural reproductive function ends, and therefore, two overlapping processes contribute to alterations in immune protection in aging women: menopause and immunosenescence. The goal of this review is to summarize the multiple immune changes that occur in the FRT with aging, including the impact on the function of epithelial cells, immune cells, and stromal fibroblasts. These studies indicate that major aspects of innate and adaptive immunity in the FRT are compromised in a site‐specific manner in the FRT as women age. Further, at some FRT sites, immunological compensation occurs. Overall, alterations in mucosal immune protection contribute to the increased risk of sexually transmitted infections (STI), urogenital infections, and gynecological cancers. Further studies are essential to provide a foundation for the development of novel therapeutic interventions to restore immune protection and reverse conditions that threaten women''s lives as they age. 相似文献
112.
Angela Haczku 《Respiratory research》2012,13(1):80
The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung. 相似文献
113.
Synaptic clusters on dendrites are extraordinarily compact computational building blocks. They contribute to key local computations through biophysical and biochemical signaling that utilizes convergence in space and time as an organizing principle. However, these computations can only arise in very special contexts. Dendritic cluster computations, their highly organized input connectivity, and the mechanisms for their formation are closely linked, yet these have not been analyzed as parts of a single process. Here, we examine these linkages. The sheer density of axonal and dendritic arborizations means that there are far more potential connections (close enough for a spine to reach an axon) than actual ones. We see how dendritic clusters draw upon electrical, chemical, and mechano–chemical signaling to implement the rules for formation of connections and subsequent computations. Crucially, the same mechanisms that underlie their functions also underlie their formation. 相似文献
114.
Retinal ganglion cell dendritic development and its control 总被引:2,自引:0,他引:2
Richard J. T. Wingate 《Molecular neurobiology》1996,12(2):133-144
The way in which central neurons acquire their complex and precise dendrite arbors is of considerable developmental interest.
Using retinal ganglion cells (RGCs) as a model, the mechanisms that pattern dendritic development are beginning to emerge.
As in other systems, final dendrite phenotype is achieved by a mixture of intrinsic and extrinsic determinants. The extrinsic
determinants of RGC dendrite shape reflect the anatomical constraints of producing a paracrystalline mosaic of arbors that
laminates the inner plexiform layer of the retina. In this article, the key features of RGC dendrite development are reviewed.
The emerging molecular mechanisms behind dendritic laminar segregation and “dendritic competition” are described. The role
of afferent extrinsic influences are contrasted with those of retrograde, activity-dependent target influences that may regulate
the final maturational phase of dendrite remodeling. 相似文献
115.
D. Bellavia L. Raimondi V. Costa A. De Luca V. Carina M. Maglio M. Fini R. Alessandro G. Giavaresi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1893-1901
Background
Exosomes are nanovesicles actively secreted by potentially all cell types, including tumour cells, with the primary role of extracellular systemic communication mediators, both at autocrine and paracrine levels, at short and long distances. Recently, different studies have used exosomes as a delivery system for a plethora of different molecules, such as drugs, microRNAs and proteins. This has been made possible thanks to the simplicity in exosomes engineering, their great stability and versatility for applications in oncology as well as in regenerative medicine.Scope of review
The aim of this review is to provide information on the state-of-the-art and possible applications of engineered exosomes, both for cargo and specific cell-targeting, in different pathologies related to the musculoskeletal system.Major conclusions
The use of exosomes as therapeutic agents is rapidly evolving, different studies explore drug delivery with exosomes using different molecules, showing an enormous potential in various research fields such as oncology and regenerative medicine.General significance
However, despite the significant progress made by the different studies carried out, currently, the use of exosomes is not a therapeutic reality for the considerable difficulties to overcome. 相似文献116.
LeMing Jiang DanFei Huang ShaoPing Nie MingYong Xie 《Saudi Journal of Biological Sciences》2018,25(6):1202-1207
Plantago species are used as traditional medicine in Asian and Europe. Polysaccharide isolated from the seeds of Plantago asiatica L. could stimulate maturation transformation of bone-marrow derived dendritic cells (DCs). We found that blocking p38, ERK1/2 and JNK MAPK signal transduction could significantly decreased the PLP-2 induced expression of MHC II, CD86 surface molecules on DCs. Blocking p38 and JNK signal also significantly inhibited the cytokine secretion of TNF-α and IL-12p70 as well, while blocking ERK1/2 signal only decreased the secretion of TNF-α. Meanwhile, DCs in the three MAPK signal-blocking groups showed dramatically attenuated effects on stimulating proliferation of T lymphocytes. Similarly, blocking signal transduction of NF-κB pathway also significantly impaired the phenotypic and functional maturation development of DCs induced by PLP-2. These data suggest that MAPK and NF-κB pathway mediates the PLP-induced maturation on DCs. Especially, among the three MAPK pathways, activation of JNK signal transduction is the most important for DCs development after PLP-2 incubation. And PLP-2 may activate the MAPK and NF-κB pathway by triggering toll-like receptor 4 on DCs. 相似文献
117.
118.
Dongliang Zhang Wei Hu Jiangang Xie Yuan Zhang Bo Zhou Xueqin Liu Yun Zhang Yingjun Su Boquan Jin Shuzhong Guo Ran Zhuang 《生物化学与生物物理学报:疾病的分子基础》2018,1864(9):3085-3098
Graft-versus-host disease (GVHD) is the most common complication and major limitation of allogeneic hematopoietic stem cell transplantation. The CD226/TIGIT-CD155 signal is critical for the cross-talk between T cells and dendritic cells (DCs). Studies have shown that blockade of the CD226-CD155 interaction, using an anti-CD226 antibody, can significantly ameliorate GVHD. It has also been reported that a TIGIT-Fc fusion protein exerts immunosuppressive effects by binding to CD155 on DCs. Here, we used a mouse allogeneic acute GVHD model to explore the therapeutic potential and mechanism of action of TIGIT-Fc. C57/BL6 and Balb/c mice were used as hematopoietic cell graft donors and recipients, respectively. In the TIGIT-Fc-treated mice, GVHD symptom occurrence and mortality were delayed compared to that in isotype control group mice. Histopathological analyses revealed that following TIGIT-Fc treatment, liver and small intestine tissue damage was reduced with minimal lymphocytic infiltration. The percentage of CD8+IFN-γ+ and CD8+ granzyme B+ cells significantly decreased in the TIGIT-Fc group. Moreover, treatment with TIGIT-Fc, even after the onset of GVHD, ameliorated symptoms and prolonged survival. TIGIT-Fc also inhibited CD8+ T cell activation in vitro; this was dependent on the presence of CD155 on bone marrow-derived dendritic cells (BMDCs) and on IL-10 production. In addition, TIGIT–CD155 ligation triggered both Erk phosphorylation and STAT3 nuclear translocation. These data indicate that TIGIT plays an important role in the development of GVHD and is an ideal molecular target to treat acute GVHD. 相似文献
119.
Ian F. Hermans Angela Daish Pisana Moroni-Rawson F. Ronchese 《Cancer immunology, immunotherapy : CII》1997,44(6):341-347
Dendritic cells (DC) purified from murine spleen or generated in vitro from bone marrow precursors were compared for their
respective abilities to stimulate T cell responses and provide tumor protection in vivo. In vitro incubation with synthetic
tumor peptide conferred on both DC populations the ability to induce proliferation of tumor-peptide-specific T cells in vitro.
Spleen DC were reproducibly about twofold more effective than bone-marrow-derived DC in this assay. Both DC populations could
also induce cytotoxic activity in vivo. In vitro cytoxicity assays showed that, while cytotoxic activity induced by immunization
with spleen DC was clearly peptide-specific, a high non-specific cytotoxic activity was consistently observed after immunization
with bone-marrow-derived DC, whether peptide-pulsed or not. Regardless of such high non-specific activity in vitro, only tumor-peptide-pulsed
DC could provide protection against subsequent inoculation of tumor cells. DC not pulsed with tumor peptide were ineffective.
We conclude that DC isolated from spleen or generated in vitro from bone marrow precursors are suitable reagents for use in
tumor vaccination studies.
Received: 13 March 1997 / Accepted: 25 May 1997 相似文献
120.
Mathieu Marc Lehmann Christian Razaname Alain Tuchscherer Gabriele 《International journal of peptide research and therapeutics》1997,4(2):95-100
Summary The assembly of helical and β-sheet peptide blocks containing reactive chain ends results in highly branched chain architectures
(‘locked-in folds’) mimicking native tertiary structures. This molecular kit strategy allows to bypass the protein folding
problem in protein de novo design and gives access to protein mimetics of high thermodynamic stability. The validity of this
concept is exemplified for the design and synthesis of locked-in folds mimicking the zinc finger and MHC folding motifs. 相似文献