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Immunoglobulin-like Transcript (immunoglobulin-like + transcript)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007
Christian
Abstract Effects of IL-10 on endothelium-dependent T cell activation have not been investigated in detail. We confirm expression of the IL-10 receptor and effective signaling via STAT-3 in human umbilical vein endothelial cells (HUVEC). In CD4 T cell cocultures with HUVEC, pretreatment of endothelial cells with IL-10 resulted in significant dose-dependent inhibition of CD4 T cell proliferation, which also occurred when IL-10 was removed after pretreatment before starting cocultures. Th1/Th2 polarization of proliferated T cells, endothelial nitric oxide (NO), or IL-12 production were unchanged. However, IL-10 stimulation resulted in up-regulation of SOCS-3, a negative regulator of cytokine secretion, and induction of the inhibitory surface molecules immunoglobulin-like transcript 3 and 4 (ILT3/ILT4) in EC, potentially involving glucocorticoid-induced leucine zipper (GILZ). Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation. In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation. No induction of foxp3+ regulatory T cells was seen. In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL-10 due to up-regulation of ILT3/ILT4, obviously not involving generation of Treg. This identifies a novel action of IL-10 in EC and a potential therapeutical target for local immunomodulation. [source]

The genomic context of natural killer receptor extended gene families

IMMUNOLOGICAL REVIEWS, Issue 1 2001
John Trowsdale
Summary: The two sets of inhibitory and activating natural killer (NK) receptor genes belong either to the Ig or to the C-type lectin superfamilies. Both are extensive and diverse, comprising genes of varying degrees of relatedness, indicative of a process of iterative duplication. We have constructed gene maps to help understand how and when NK receptor genes developed and the nature of their polymorphism. A cluster of over 15 C-type lectin genes, the natural killer complex is located on human chromosome 12p13.1, syntenic with a region in mouse that borders multiple Ly49 loci. The equivalent locus in man is occupied by a single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer cell immunoglobulin-like receptor (KIR) genes as well as multiple related sequences. These include immunoglobulin-like transcript (ILT) (or leukocyte immunoglobulin-like receptor genes), leukocyte-associated inhibitory receptor genes (LAIR), NKp46, Fc,R and the platelet glycoprotein receptor VI locus, which encodes a collagen-binding molecule. KIRs are expressed mostly on NK cells and some T cells. The other LRC loci are more widely expressed. Further centromeric of the LRC are sets of additional loci with weak sequence similarity to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC-syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes are highly polymorphic in terms of sequence as well as for presence/absence of genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only ILT6 exhibits presence/absence variation. This knowledge of the genomic organisation of the extensive NK superfamilies underpins efforts to understand the functions of the encoded NK receptor molecules. It leads to the conclusion that the functional homology of human KIR and mouse Ly49 genes arose by convergent evolution. NK receptor immunogenetics has interesting parallels with the major histocompatibility complex (MHC) in which some of the polymorphic genes are ligands for NK molecules. There are hints of an ancient genetic relationship between NK receptor genes and MHC-paralogous regions on chromosomes 1, 9 and 19. The picture that emerges from both complexes is of eternal evolutionary restlessness, presumably in response to resistance to disease. This work was funded by the Wellcome Trust and the MRC [source]

Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex

IMMUNOLOGICAL REVIEWS, Issue 1 2001
Armin Volz
Summary: The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily. The genes include two clusters of immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LIR)/monocyte-macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitory receptor (KIR) genes, two leukocyte-associated immunoglobulin-like receptor genes, as well as the Fc receptor for IgA and the natural cytotoxicity receptor 1 loci. It has already been postulated that these genes have evolved by multiple duplications, while the two ILT clusters are likely to have been generated by the inverse duplication of an ancient ILT cluster. To shed more light on the possible origin of the loci within the LRC, we have now investigated the presence of KIR and ILT loci in a variety of vertebrates by hybridizations and compared the genomic sequences of all ILT genes. Our results lead to the following conclusions: 1) the origin of KIR genes dates back to about 100 million years, but only primate and human KIRs are closely related; 2) in contrast, genes which are detectable with human ILT cDNAs are already found in birds, suggesting their presence already about 300 million years ago. Using the sequence data produced by the human genome project, we have developed a hypothesis that reconstructs the genesis of the two human ILT clusters in detail which will help to understand the function of the LRC. This work was supported by the European Union through grant BMH4-CT96,1105 (to A.Z.). We also thank the Sonnenfeld-Stiftung (Berlin) and the Berliner Krebsgesellschaft for financial support. [source]

Association of immunoglobulin-like transcript 6 deficiency with Sjögren's syndrome

ARTHRITIS & RHEUMATISM, Issue 10 2009
G. Kabalak
Objective The immunoglobulin-like transcript (ILT) family is located in chromosomal region 19q13 and consists of a group of activating and inhibitory receptors. The ILT receptors are expressed on antigen-presenting cells (macrophages, dendritic cells, B lymphocytes), as well as on T cells and natural killer cells. ILT2 and ILT4 play a role in tolerance induction, and ILT3 has been shown to induce Treg cells. A homozygous deletion of ILT6 has been shown to be associated with multiple sclerosis. Since ILT6 may be a modulator of the immune system, we undertook this study to examine the association of ILT6 deficiency with Sjögren's syndrome (SS). Methods We genotyped 149 patients with SS and 749 healthy controls, using polymerase chain reaction to test for the presence or absence of ILT6. Results Homozygous ILT6 deficiency was detected in 8% of SS patients and in only 3% of controls. Conclusion Our findings indicate that ILT6 deficiency may be a genetic risk factor for SS. [source]