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1.
Kiave-Yune HoWangYin Maria Loustau Juan Wu Estibaliz Alegre Marina Daouya Julien Caumartin Sylvie Sousa Anatolij Horuzsko Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2012,69(23):4041-4049
The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α1–α2–α3 non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α1–α3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α1–α3-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents. 相似文献
2.
Carosella ED Gregori S Rouas-Freiss N LeMaoult J Menier C Favier B 《Cellular and molecular life sciences : CMLS》2011,68(3):353-368
The non-classical HLA class I molecule HLA-G was initially shown to play a major role in feto–maternal tolerance. Since this
discovery, it has been established that HLA-G is a tolerogenic molecule which participates to the control of the immune response.
In this review, we summarize the recent advances on (1) the multiple structures of HLA-G, which are closely associated with
their role in the inhibition of NK cell cytotoxicity, (2) the factors that regulate the expression of HLA-G and its receptors,
(3) the mechanism of action of HLA-G at the immunological synapse and through trogocytosis, and (4) the generation of suppressive
cells through HLA-G. Moreover, we also review recent findings on the non-immunological functions of HLA-G in erythropoiesis
and angiogenesis. 相似文献
3.
Immunotolerant functions of HLA-G 总被引:9,自引:0,他引:9
Carosella ED Dausset J Rouas-Freiss N 《Cellular and molecular life sciences : CMLS》1999,55(3):327-333
4.
Rizzo R Vercammen M van de Velde H Horn PA Rebmann V 《Cellular and molecular life sciences : CMLS》2011,68(3):341-352
The nonclassical HLA-G molecule is a trophoblast-specific molecule present in almost every pregnancy. It differs from classical
HLA class I molecules by the low degree of allelic variants and the high diversity of protein structures. HLA-G is reported
to be a tolerogenic molecule that acts on cells of both innate and adaptive immunity. At the maternal–fetal interface HLA-G
seems to be responsible largely for the reprogramming of local maternal immune response. This review will focus on the HLA-G
gene expression profile in pregnancy, in preimplantation embryos, and in human embryonic stem cells with emphasis on the structural
diversity of the HLA-G protein and its potential functional and diagnostic implications. 相似文献
5.
6.
Moreau P Rousseau P Rouas-Freiss N Le Discorde M Dausset J Carosella ED 《Cellular and molecular life sciences : CMLS》2002,59(9):1460-1466
Data are presented on the intracellular trafficking of HLA-G protein, taking the unique features of this non-classical molecule
into consideration: the existence of seven isoforms resulting from alternative splicing (HLA-G1 to G7), and reduced tail length
compared with HLA class I antigens. Biochemical studies and analysis of viral strategies for escaping the host immune system
led to the demonstration that (i) both the membrane-bound (HLA-G1) and the soluble (HLA-G5) forms of the molecule require
peptide association for cell surface expression, using TAP-dependent or TAP-independent pathways; (ii) peptide loading onto
the HLA-G protein plays a critical role in controlling the quality of the molecule reaching the cell surface; (iii) surface
expression of truncated HLA-G molecules is possible, and (iv) HLA-G expression may be restricted to soluble HLA-G5. These
data reveal that HLA-G presents specific cell trafficking pathways and strongly support the contention that the primary function
of HLA-G is as of an inhibitor ligand for immune-competent cells.
Received 4 June 2002; accepted 2 July 2002
RID="*"
ID="*"Corresponding author. 相似文献
7.
Lesport E Baudhuin J Sousa S LeMaoult J Zamborlini A Rouas-Freiss N Carosella ED Favier B 《Cellular and molecular life sciences : CMLS》2011,68(20):3385-3399
Vγ9Vδ2 T cells play a crucial role in the antitumoral immune response through cytokine production and cytotoxicity. Although
the expression of the immunomodulatory molecule HLA-G has been found in diverse tumors, its impact on Vγ9Vδ2 T-cell functions
remains unknown. Here we showed that soluble HLA-G inhibits Vγ9Vδ2 T-cell proliferation without inducing apoptosis. Moreover,
soluble HLA-G inhibited the Vγ9Vδ2 T-cell production of IFN-γ induced by phosphoantigen stimulation. The reduction in Vγ9Vδ2
T-cell IFN-γ production was also induced by membrane-bound or soluble HLA-G expressed by tumor cell lines. Finally, primary
tumor cells inhibited Vγ9Vδ2 T-cell proliferation and IFN-γ production through HLA-G. In this context, HLA-G impaired Vγ9Vδ2
T-cell cytotoxicity by interacting with ILT2 inhibitory receptor. These data demonstrate that HLA-G inhibits the anti-tumoral
functions of Vγ9Vδ2 T cells and imply that treatments targeting HLA-G could optimize Vγ9Vδ2 T-cell-mediated immunotherapy
of cancer. 相似文献
8.
Alais S Soto-Rifo R Balter V Gruffat H Manet E Schaeffer L Darlix JL Cimarelli A Raposo G Ohlmann T Leblanc P 《Cellular and molecular life sciences : CMLS》2012,69(8):1331-1352
The cellular prion protein PrP(C)/CD230 is a GPI-anchor protein highly expressed in cells from the nervous and immune systems and well conserved among vertebrates. In the last decade, several studies suggested that PrP(C) displays antiviral properties by restricting the replication of different viruses, and in particular retroviruses such as murine leukemia virus (MuLV) and the human immunodeficiency virus type 1 (HIV-1). In this context, we previously showed that PrP(C) displays important similarities with the HIV-1 nucleocapsid protein and found that PrP(C) expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrP(C) mutants, we report here that the anti-HIV-1 properties are mostly associated with the amino-terminal 24-KRPKP-28 basic domain. In agreement with its reported RNA chaperone activity, we found that PrP(C) binds to the viral genomic RNA of HIV-1 and negatively affects its translation. Using a combination of biochemical and cell imaging strategies, we found that PrP(C) colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrP(C) in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle. 相似文献
9.
More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell
from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular
matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration,
and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized,
opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles
in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during
development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components
with a special emphasis on embryonic and adult stem cells and their niches. 相似文献
10.
Pierfrancesco Pagella Lucia Jiménez-Rojo Thimios A. Mitsiadis 《Cellular and molecular life sciences : CMLS》2014,71(12):2241-2251
The head is innervated by 12 cranial nerves (I–XII) that regulate its sensory and motor functions. Cranial nerves are composed of sensory, motor, or mixed neuronal populations. Sensory neurons perceive generally somatic sensations such as pressure, pain, and temperature. These neurons are also involved in smell, vision, taste, and hearing. Motor neurons ensure the motility of all muscles and glands. Innervation plays an essential role in the development of the various orofacial structures during embryogenesis. Hypoplastic cranial nerves often lead to abnormal development of their target organs and tissues. For example, Möbius syndrome is a congenital disease characterized by defective innervation (i.e., abducens (VI) and facial (VII) nerves), deafness, tooth anomalies, and cleft palate. Hence, it is obvious that the peripheral nervous system is needed for both development and function of orofacial structures. Nerves have a limited capacity to regenerate. However, neural stem cells, which could be used as sources for neural tissue maintenance and repair, have been found in adult neuronal tissues. Similarly, various adult stem cell populations have been isolated from almost all organs of the human body. Stem cells are tightly regulated by their microenvironment, the stem cell niche. Deregulation of adult stem cell behavior results in the development of pathologies such as tumor formation or early tissue senescence. It is thus essential to understand the factors that regulate the functions and maintenance of stem cells. Yet, the potential importance of innervation in the regulation of stem cells and/or their niches in most organs and tissues is largely unexplored. This review focuses on the potential role of innervation in the development and homeostasis of orofacial structures and discusses its possible association with stem cell populations during tissue repair. 相似文献
11.
The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation 总被引:8,自引:0,他引:8
J Auwerx 《Experientia》1991,47(1):22-31
THP-1 is a human monocytic leukemia cell line. After treatment with phorbol esters, THP-1 cells differentiate into macrophage-like cells which mimic native monocyte-derived macrophages in several respects. Compared to other human myeloid cell lines, such as HL-60, U937, KG-1, or HEL cell lines, differentiated THP-1 cells behave more like native monocyte-derived macrophages. Because of these characteristics, the THP-1 cell line provides a valuable model for studying the mechanisms involved in macrophage differentiation, and for exploring the regulation of macrophage-specific genes as they relate to physiological functions displayed by these cells. 相似文献
12.
J. Auwerx 《Cellular and molecular life sciences : CMLS》1991,47(1):22-31
Summary THP-1 is a human monocytic leukemia cell line. After treatment with phorbol esters, THP-1 cells differentiate into macrophage-like cells which mimic native monocyte-derived macrophages in several respects. Compared to other human myeloid cell lines, such as HL-60, U937, KG-1, or HEL cell lines, differentiated THP-1 cells behave more like native monocyte-derived macrophages. Because of these characteristics, the THP-1 cell line provides a valuable model for studying the mechanisms involved in macrophage differentiation, and for exploring the regulation of macrophage-specific genes as they relate to physiological functions displayed by these cells. 相似文献
13.
14.
The neurotrophic factors in non-neuronal tissues 总被引:17,自引:0,他引:17
Sariola H 《Cellular and molecular life sciences : CMLS》2001,58(8):1061-1066
Although neurotrophic factors are defined as molecules that maintain neuronal cells, they possess a range of functions outside
the nervous system. For example, glial cell line-derived neurotrophic factor is essential for ureteric branching in kidney
morphogenesis and for regulating the fate of stem cells during spermatogenesis. Leukemia inhibitory factor, a member of the
interleukin-6 (IL-6) ciliary neurotrophic factor family, inhibits differentiation of embryonic stem cells, induces tubulogenesis
in the embryonic kidney, and regulates sperm differentiation. Other IL-6 family members are important in cardiac differentiation
and they have pleiotropic functions in the hematopoietic and immune systems. Although neurotrophin receptors have been found
on a number of non-neuronal tissues, they represent mostly truncated receptor isoforms that are incapable of signal transduction
and may have scavenger or dominant negative functions. However, several examples can be presented of essential non-neuronal
functions played by neurotrophins in e.g., cardiac, hair follicle, and vascular differentiation, and the maintenance of immune
cells. 相似文献
15.
Chemokines are a vertebrate-specific group of small molecules that regulate cell migration and behaviour in diverse contexts.
So far, around 50 chemokines have been identified in humans, which bind to 18 different chemokine receptors. These are members
of the seven-transmembrane receptor family. Initially, chemokines were identified as modulators of the immune response. Subsequently,
they were also shown to regulate cell migration during embryonic development. Here, we discuss the influence of chemokines
and their receptors on angiogenesis, or the formation of new blood vessels. We highlight recent advances in our understanding
of how chemokine signalling might directly influence endothelial cell migration. We furthermore examine the contributions
of chemokine signalling in immune cells during this process. Finally, we explore possible implications for disease settings,
such as chronic inflammation and tumour progression. 相似文献
16.
Kiave-Yune HoWangYin Estibaliz Alegre Marina Daouya Benoit Favier Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2010,67(7):1133-1145
Trogocytosis is the uptake of membranes from one cell by another. Trogocytosis has been demonstrated for monocytes, B cells,
T cells, and NK cells. The acquisition of the tolerogenic molecule HLA-G by T cells and NK cells makes them behave as regulatory
cells. We investigated here whether HLA-G, which is expressed by tumor cells in vivo, could be acquired by monocytes and if
this transfer could have functional consequences. We demonstrate that resting, and even more so, activated monocytes efficiently
acquire membrane-bound HLA-G from HLA-G tumor cells by trogocytosis. However, we demonstrate that HLA-G quickly disappears
from the surface of the monocytes in contrast to the HLA-G acquired by T cells. Consequently, HLA-Gacq+ monocytes do not reliably inhibit the on-going proliferation of autologous activated T cells and do not inhibit their cytokine
production. Thus, we show that the acquirer cell may control the functional outcome of trogocytosis. 相似文献
17.
Deschaseaux F Delgado D Pistoia V Giuliani M Morandi F Durrbach A 《Cellular and molecular life sciences : CMLS》2011,68(3):397-404
HLA-G plays a particular role during pregnancy in which its expression at the feto–maternal barrier participates into the
tolerance of the allogenic foetus. HLA-G has also been demonstrated to be expressed in some transplanted patients, suggesting
that it regulates the allogenic response. In vitro data indicate that HLA-G modulates NK cells, T cells, and DC maturation
through its interactions with various inhibitory receptors. In this paper, we will review the data reporting the HLA-G involvement
of HLA-G in human organ transplantation, then factors that can modulate HLA-G, and finally the use of HLA-G as a therapeutic
tool in organ transplantation. 相似文献
18.
Wesch D Peters C Oberg HH Pietschmann K Kabelitz D 《Cellular and molecular life sciences : CMLS》2011,68(14):2357-2370
Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules
derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to
subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several
T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the
recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T
cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast
to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine
production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via
TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands
indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human
tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated
signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly
or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity
of γδ T cells. 相似文献
19.
C. Sauter 《Cellular and molecular life sciences : CMLS》1989,45(6):594-596
Summary Influenza A viruses grown in different animal or human cells retain their antigenic make-up as tested by the usual immunological assays. With the aid of aSambucus nigra (L.) extract containing its lectins the viruses can be distinguished after one single passage in a different cell type by a change in their hemagglutinating properties. Binding of such lectins to influenza viruses may be a means for a more subtle classification, relating to the host cell origin of the virus. 相似文献