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1.
Intestinal epithelial barrier and mucosal immunity 总被引:6,自引:0,他引:6
The mucosal immune system maintains a delicate balance between providing robust defense against infectious pathogens and, at the same time, regulating responses toward innocuous environmental and food antigens and commensal microbes. The Peyer's patch (PP) has been studied in detail as a major inductive site for mucosal immunity within the small intestine. While the mechanisms responsible for the induction of mucosal immunity versus tolerance are not yet fully understood, recent studies have highlighted mucosal dendritic cells (DCs) as regulators of the immune responses to orally administered antigens. Here we discuss recent studies that describe the role of PP DCs in immune induction and speculate on the mechanism by which the resident DCs regulate T cell and immunoglobulin A (IgA) responses in the gastrointestinal mucosa. 相似文献
2.
M. Rakhshandehroo E. Kalkhoven M. Boes 《Cellular and molecular life sciences : CMLS》2013,70(24):4711-4727
Adipose tissue (AT) represents a microenvironment where intersection takes place between immune processes and metabolic pathways. A variety of immune cells have been characterized in AT over the past decades, with the most recent addition of invariant natural killer T (iNKT) cells. As members of the T cell family, iNKT cells represent a subset that exhibits both innate and adaptive characteristics and directs ensuing immune responses. In disease conditions, iNKT cells have established roles that include disorders in the autoimmune spectrum in malignancies and infectious diseases. Recent work supports a role for iNKT cells in the maintenance of AT homeostasis through both immune and metabolic pathways. The deficiency of iNKT cells can result in AT metabolic disruptions and insulin resistance. In this review, we summarize recent work on iNKT cells in immune regulation, with an emphasis on AT-resident iNKT cells, and identify the potential mechanisms by which adipocytes can mediate iNKT cell activity. 相似文献
3.
Infectious tolerance is a process whereby one regulatory lymphoid population confers suppressive capacity on another. Diverse immune responses are induced following infection or inflammatory insult that can protect the host, or potentially cause damage if not properly controlled. Thus, the process of infectious tolerance may be critical in vivo for exerting effective immune control and maintaining immune homeostasis by generating specialized regulatory sub-populations with distinct mechanistic capabilities. Foxp3(+) regulatory T cells (T(regs)) are a central mediator of infectious tolerance through their ability to convert conventional T cells into induced regulatory T cells (iT(regs)) directly by secretion of the suppressive cytokines TGF-β, IL-10, or IL-35, or indirectly via dendritic cells. In this review, we will discuss the mechanisms and cell populations that mediate and contribute to infectious tolerance, with a focus on the intestinal environment, where tolerance induction to foreign material is critical. 相似文献
4.
The murine epidermis contains resident T cells that express a canonical γδ TCR and arise from fetal thymic precursors. These
cells are termed dendritic epidermal T cells (DETC) and use a TCR that is restricted to the skin in adult animals. DETC produce
low levels of cytokines and growth factors that contribute to epidermal homeostasis. Upon activation, DETC can secrete large
amounts of inflammatory molecules which participate in the communication between DETC, neighboring keratinocytes and langerhans
cells. Chemokines produced by DETC may recruit inflammatory cells to the epidermis. In addition, cell–cell mediated immune
responses also appear important for epidermal–T cell communication. Information is provided which supports a crucial role
for DETC in inflammation, wound healing, and tumor surveillance. 相似文献
5.
Cytotoxic (CD8+) and helper (CD4+) T cells play a crucial role in resolving infections by intracellular pathogens. The development of technologies to visualize
antigen-specific T cell responses in mice and men over the past decade has allowed a dissection of the formation of adaptive
T cell immunity. This review gives a brief overview of the currently used detection techniques and possible future additions.
Furthermore, we discuss our current understanding of the formation of antigen-specific T cell responses, with particular attention
to the similarities and differences in CD4+ and CD8+ T cell responses, the functional heterogeneity within responder T cell pools and the regulation of CD8+ T cell responses by dendritic cells and CD4+ helper T cells.
Received 16 June 2005; received after revision 2 August 2005; accepted 15 August 2005 相似文献
6.
Multi-layered regulation of intestinal antimicrobial defense 总被引:1,自引:0,他引:1
Mukherjee S Vaishnava S Hooper LV 《Cellular and molecular life sciences : CMLS》2008,65(19):3019-3027
7.
The role of the proteasome in the generation of MHC class I ligands and immune responses 总被引:2,自引:2,他引:0
The ubiquitin–proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major
histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition
differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory
cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome
activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of
thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class
I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions
of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses. 相似文献
8.
9.
L. Adorini 《Cellular and molecular life sciences : CMLS》1999,55(12):1610-1625
Interleukin 12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (APCs) which plays a key
role in promoting type 1 T helper cell (Th1) responses. The powerful activity of IL-12 requires tight control, which is exerted
at various levels. Primary control is exerted on IL-12 production by APCs, a major factor driving the response towards the
Th1 or Th2 phenotype. Another level of control regulates expression of the IL-12 receptor (IL-12R), which is composed of two
subunits, β1 and β2. The IL-12R β2 subunit has signal-transducing capacity and modulation of its expression is central to
the regulation of IL-12 responsiveness. Endogenous IL-12 plays an important role in host defense against infection by a variety
of intracellular pathogens. Its Th1-promoting activity, however, also favors Th1-mediated immunopathology and, in particular,
the induction of Th1-mediated autoimmune diseases.
Received 15 January 1999; received after revision 11 March 1999; accepted 16 March 1999 相似文献
10.
The central nervous system (CNS) is considered an immune-privileged organ that maintains an adaptable immune surveillance
system. Dysregulated immune function within the CNS contributes to the development of brain tumor growth, and robust immune
activation results in excessive inflammation. Human lymphocyte antigen-G (HLA-G) proteins with tolerogenic immunoreactivity
have been implicated in various pathophysiological processes including immune surveillance, governing homeostasis and immune
regulation. In this review, we describe the wealth of evidence for the involvement of HLA-G in the CNS under physiological
and pathological conditions. Further, we review regulatory functions that may be applicable as beneficial strategies in the
therapeutic manipulation of immune-mediated CNS immune responses. Additionally, we try to understand how this molecule cooperates
with other CNS-resident cells to maintain normal immune homeostasis, while still facilitating the development of the appropriate
immune responses. 相似文献
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13.
Macpherson AJ Martinic MM Harris N 《Cellular and molecular life sciences : CMLS》2002,59(12):2088-2096
There is an immense load of non-pathogenic commensal bacteria in the distal small intestine and the colon of mammals. The
physical barrier that prevents penetration (translocation) of these organisms into the body is a simple epithelium comprised
of the single enterocyte/colonocyte cell layer with its overlying mucus. In this review, we discuss the roles of intestinal
T cells in initiating and regulating innate and adaptive mucosal immune responses of the mucosal immune system that avoid
or limit penetration of the commensal intestinal bacteria.
Received 9 August 2002; accepted 9 September 2002
RID="*"
ID="*"Corresponding author. 相似文献
14.
Syed Zahid Ali Shah Tariq Hussain Deming Zhao Lifeng Yang 《Cellular and molecular life sciences : CMLS》2017,74(6):1061-1074
Accumulation of misfolded/unfolded aggregated proteins in the brain is a hallmark of many neurodegenerative diseases affecting humans and animals. Dysregulation of calcium (Ca2+) and disruption of fast axonal transport (FAT) are early pathological events that lead to loss of synaptic integrity and axonal degeneration in early stages of neurodegenerative diseases. Dysregulated Ca2+ in the brain is triggered by accumulation of misfolded/unfolded aggregated proteins in the endoplasmic reticulum (ER), a major Ca2+ storing organelle, ultimately leading to neuronal dysfunction and apoptosis. Calcineurin (CaN), a Ca2+/calmodulin-dependent serine/threonine phosphatase, has been implicated in T cells activation through the induction of nuclear factor of activated T cells (NFAT). In addition to the involvement of several other signaling cascades, CaN has been shown to play a role in early synaptic dysfunction and neuronal death. Therefore, inhibiting hyperactivated CaN in early stages of disease might be a promising therapeutic strategy for treating patients with protein misfolding diseases. In this review, we briefly summarize the structure of CaN, inhibition mechanisms by which immunosuppressants inhibit CaN, role of CaN in maintaining neuronal and synaptic integrity and homeostasis and the role played by CaN in protein unfolding/misfolding neurodegenerative diseases. 相似文献
15.
Gereben B Zeöld A Dentice M Salvatore D Bianco AC 《Cellular and molecular life sciences : CMLS》2008,65(4):570-590
The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting
the expression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control
thyroid hormone action by activating or inactivating the precursor molecule thyroxine that is secreted by the thyroid gland.
These pathways ensure regulation of the availability of the biologically active molecule T3, which occurs in a time-and tissue-specific
fashion. In addition, because cells and plasma are in equilibrium and deiodination affects central thyroid hormone regulation,
these local deiodinase-mediated events can also affect systemic thyroid hormone economy, such as in the case of non-thyroidal
illness. Heightened interest in the field has been generated following the discovery that the deiodinases can be a component
in both the Sonic hedgehog signaling pathway and the TGR-5 signaling cascade, a G-protein-coupled receptor for bile acids.
These new mechanisms involved in deiodinase regulation indicate that local thyroid hormone activation and inactivation play
a much broader role than previously thought.
Received 29 August 2007; received after revision 11 October 2007; accepted 16 October 2007 相似文献
16.
Daniel A. Winer Shawn Winer Melissa H. Y. Chng Lei Shen Edgar G. Engleman 《Cellular and molecular life sciences : CMLS》2014,71(6):1033-1043
Obesity-related insulin resistance is a chronic inflammatory condition that often gives rise to type 2 diabetes (T2D). Much evidence supports a role for pro-inflammatory T cells and macrophages in promoting local inflammation in tissues such as visceral adipose tissue (VAT) leading to insulin resistance. More recently, B cells have emerged as an additional critical player in orchestrating these processes. B cells infiltrate VAT and display functional and phenotypic changes in response to diet-induced obesity. B cells contribute to insulin resistance by presenting antigens to T cells, secreting inflammatory cytokines, and producing pathogenic antibodies. B cell manipulation represents a novel approach to the treatment of obesity-related insulin resistance and potentially to the prevention of T2D. This review summarizes the roles of B cells in governing VAT inflammation and the mechanisms by which these cells contribute to altered glucose homeostasis in insulin resistance. 相似文献
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18.
Dendritic cells (DCs) are a heterogeneous cell population of great importance in the immune system. The emergence of new genetic technology utilizing the CD11c promoter and Cre recombinase has facilitated the dissection of functional significance and molecular regulation of DCs in immune responses and homeostasis in vivo. For the first time, this strategy allows observation of the effects of DC-specific gene deletion on immune system function in an intact organism. In this review, we present the latest findings from studies using the Cre recombinase system for cell type-specific deletion of key molecules that mediate DC homeostasis and function. Our focus is on the molecular pathways that orchestrate DC life span, migration, antigen presentation, pattern recognition, and cytokine production and signaling. 相似文献
19.
Intestinal epithelial barrier and mucosal immunity 总被引:3,自引:0,他引:3
Dubois B Goubier A Joubert G Kaiserlian D 《Cellular and molecular life sciences : CMLS》2005,62(12):1322-1332
Regulated mechanisms sustain the ability of the gut immune system to discriminate harmless food antigens (Ag) and commensal bacteria from pathogenic microorganisms, resulting in tolerance versus protective immunity, respectively. Antigens of the gut commensals are not simply ignored, but rather trigger an active immunosuppressive process, more commonly known as oral tolerance, which prevents the outcome of immunopathology. Both intrinsic properties of the gut microenvironment and cellular actors, as well as peripheral events induced by systemic dissemination of oral Ag, promote the induction of regulatory mechanisms that ensure maintenance of gut homeostasis. The aim of this review is to provide a synthetic update on the mechanisms of oral tolerance, with particular emphasis on the complex interplay between regulatory CD4+ T cells, dendritic cells and the gut microenvironment. 相似文献
20.
Xuezhi Kang Dongman Chao Quanbao Gu Guanghong Ding Yingwei Wang Gianfranco Balboni Lawrence H. Lazarus Ying Xia 《Cellular and molecular life sciences : CMLS》2009,66(21):3505-3516
Hypoxic/ischemic disruption of ionic homeostasis is a critical trigger of neuronal injury/death in the brain. There is, however,
no promising strategy against such pathophysiologic change to protect the brain from hypoxic/ischemic injury. Here, we present
a novel finding that activation of δ-opioid receptors (DOR) reduced anoxic Na+ influx in the mouse cortex, which was completely blocked by DOR antagonism with naltrindole. Furthermore, we co-expressed
DOR and Na+ channels in Xenopus oocytes and showed that DOR expression and activation indeed play an inhibitory role in Na+ channel regulation by decreasing the amplitude of sodium currents and increasing activation threshold of Na+ channels. Our results suggest that DOR protects from anoxic disruption of Na+ homeostasis via Na+ channel regulation. These data may potentially have significant impacts on understanding the intrinsic mechanism of neuronal
responses to stress and provide clues for better solutions of hypoxic/ischemic encephalopathy, and for the exploration of
acupuncture mechanism since acupuncture activates opioid system. 相似文献