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Lymphocyte-activation gene 3

LAG-3, CD223
Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: CD4, CD8, CTLA-4, MHC, CAN
Papers on LAG-3
Expression of PD-1/LAG-3 and cytokine production by CD4(+) T cells during infection with Plasmodium parasites.
New
Yui et al., Nagasaki, Japan. In Microbiol Immunol, Jan 2016
CD4(+) T cells from mice infected with P. yoelii 17XL, P yoelii 17XNL, P. chabaudi, P. vinckei, and P. berghei expressed the inhibitory receptors, PD-1 and LAG-3 as early as 6 days after infection, while those from either Listeria monocytogenes or Leishmania major-infected mice did not.
Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression.
New
Mandruzzato et al., Padova, Italy. In Oncotarget, Jan 2016
Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction.
Targeting immune checkpoints: New opportunity for mesothelioma treatment?
Review
New
Smits et al., Antwerp, Belgium. In Cancer Treat Rev, Dec 2015
Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints.
Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance.
New
Yang et al., Changchun, China. In Int J Mol Sci, Dec 2015
We demonstrated that Aire cells upregulated the mRNA levels of the tolerance-related molecules CD73, Lag3, and FR4 and the apoptosis of CD4⁺ T cells in STZ-T1D mouse-derived splenocytes.
Emerging immune checkpoints for cancer therapy.
Review
New
Wu et al., Changzhou, China. In Acta Oncol, Nov 2015
LAG-3 and TIM-3 are two new immune checkpoints.
Inhibitory receptors as targets for cancer immunotherapy.
Review
New
Vignali et al., Memphis, United States. In Eur J Immunol, Jul 2015
Tumor-specific T cells that exhibit an exhausted, unresponsive phenotype express high levels of inhibitory receptors including CTLA4, PD1, and LAG3, among others.
Toxicity patterns with immunomodulating antibodies and their combinations.
Review
New
Blank et al., Amsterdam, Netherlands. In Semin Oncol, Jun 2015
Immune checkpoint molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1), but also LAG-3 and TIM-3, are involved in regulation of peripheral tolerance in order to prevent autoimmunity.
Clinical blockade of PD1 and LAG3--potential mechanisms of action.
Review
Impact
Ohashi et al., Toronto, Canada. In Nat Rev Immunol, 2015
In this Review, we discuss the potential mechanisms of action of the clinical agents that target two of these receptors, programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 protein (LAG3).
An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells.
Hosen et al., Suita, Japan. In Plos One, 2014
In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3.
WNT5A transforms intestinal CD8αα(+) IELs into an unconventional phenotype with pro-inflammatory features.
Ran et al., Shanghai, China. In Bmc Gastroenterol, 2014
The non-canonical WNT5A skewed them into a pro-inflammatory category as measured by inhibitory cell surface marker LAG3, LY49E, NKG2A and activated marker CD69 and FASL.
[Immunotherapy for the Prevention and Treatment of Breast Cancer].
Review
Slabý et al., In Klin Onkol, 2014
CTLA-4, PD-1/ PD-L1, LAG3).
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells.
Impact
Roncarolo et al., Milano, Italy. In Nat Med, 2013
By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells.
Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.
Impact
Kuchroo et al., Boston, United States. In Nat Med, 2012
Bat3-deficient T cells have elevated expression of exhaustion-associated molecules such as Tim-3, Lag3, Prdm1 and Pbx3, and Bat3 knockdown in myelin-antigen–specific CD4+ T cells markedly inhibits the development of experimental autoimmune encephalomyelitis while promoting the expansion of a dysfunctional Tim-3hi, interferon-γ (IFN-γ)loCD4+ cell population.
Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape.
GeneRIF
Vignali et al., Memphis, United States. In Cancer Res, 2012
these results define a strong synergy between the PD-1 and LAG-3 inhibitory pathways in tolerance to both self and tumor antigens.
Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.
Impact
Harty et al., Iowa City, United States. In Nat Immunol, 2012
In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice.
Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3.
GeneRIF
Vignali et al., Memphis, United States. In J Immunol, 2011
We conclude that LAG-3 is necessary for regulating CD4(+) and CD8(+) T cell function during autoimmune diabetes
LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L.
GeneRIF
Sykes et al., Boston, United States. In Blood, 2011
LAG-3 is required for long-term peripheral CD8 but not CD4 T-cell tolerance and this requirement is CD8 cell-extrinsic.
MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis.
GeneRIF
Michel et al., Paris, France. In J Immunol, 2011
our data suggest that the LAG-3-MHC II interaction could be viewed as a bidirectional immune escape pathway in melanoma
PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice.
GeneRIF
Honjo et al., Tokushima, Japan. In J Exp Med, 2011
LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Impact
Wherry et al., Philadelphia, United States. In Nat Immunol, 2009
Regulation of T cell exhaustion by various inhibitory pathways was nonredundant, as blockade of the T cell inhibitory receptors PD-1 and LAG-3 simultaneously and synergistically improved T cell responses and diminished viral load in vivo.
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