Recombinant Mouse B- and T-lymphocyte attenuator (Btla), partial
Description
Introduction to Recombinant Mouse B- and T-Lymphocyte Attenuator (Btla), Partial
B- and T-lymphocyte attenuator (BTLA) is a co-inhibitory receptor belonging to the immunoglobulin superfamily, expressed predominantly on B and T lymphocytes . BTLA has an immunoglobulin superfamily domain in its extracellular region and immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences in its intracellular region . Its ligand, herpesvirus entry mediator (HVEM), binds as a monomeric agonist that signals through BTLA to inhibit T cell proliferation . BTLA influences the effectiveness of immunotherapies .
BTLA Expression and Function
BTLA is expressed on various immune cells, including B cells, T cells, dendritic cells, splenic macrophages, and natural killer (NK) cells . While it is absent on naive T cells, BTLA upregulates on activated T cells and remains on polarized T helper type 1 (Th1) cells in both mice and humans .
BTLA plays a crucial role in modulating immune responses:
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Immune Suppression: BTLA induces immunosuppression by inhibiting B and T cell activation and proliferation .
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T Cell Regulation: BTLA engagement on follicular T helper (Tfh) cells reduces T cell receptor (TCR) signaling and CD40 ligand mobilization, diminishing help to B cells and inhibiting their proliferation . BTLA can also inhibit IL-21 production by Tfh cells, suppressing the development of germinal center B cells and subsequent IgG responses .
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CD4+ T Cell Activation: BTLA negatively regulates B and T cell activation .
BTLA in Disease Models
BTLA's role has been investigated in various disease models, revealing its potential as a therapeutic target.
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Atherosclerosis: BTLA stimulation protects against atherosclerosis by regulating follicular B cells . BTLA stimulation in Ldlr−/− mice reduces initial lesion development and increases collagen content of established lesions, potentially by shifting the balance between atherogenic follicular B cells and atheroprotective B cells and directing CD4+ T cells towards regulatory T cells .
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Lupus: Targeting BTLA regulates lupus disease development in NZB/W mice . Administration of the 6F7 anti-BTLA antibody in NZB/W mice delayed the onset of proteinuria, limited kidney damage, and increased survival rate compared to isotype-treated mice .
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Cancer: BTLA expression is up-regulated on spontaneous NY-ESO-1–specific CD8+ T cells in patients' PBLs . BTLA+PD-1+Tim-3− cells exhibit partial T-cell dysfunction, producing more IFN-γ, TNF, and IL-2 than BTLA+PD-1+Tim-3+ cells but less IFN-γ than BTLA−PD-1+Tim-3− and BTLA−PD-1−Tim-3− NY-ESO-1–specific CD8+ T cells .
BTLA and Lipid Metabolism
Restoring lipid metabolism can rescue defective BTLA functionality . BTLA recruitment to TCR clusters was significantly lower in SLE patients compared to healthy controls (61% ± 7% in SLE vs. 87% ± 4% in HCs, P < 0.01) .
BTLA Promoter Methylation
BTLA promoter hypomethylation correlates with enhanced immune cell infiltration in melanoma . Tumors with promoter hypomethylation exhibit higher infiltration levels of various immune cells . Lower promoter methylation of BTLA predicts higher infiltration levels in melanoma .
BTLA as a Therapeutic Target
BTLA is a potential therapeutic target for treating lupus . BTLA stimulation emerges as a promising therapeutic approach for atherosclerosis .
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Target Background
- BTLA on type I NKT cells limits anti-tumor immunity. PMID: 29518903
- HVEM/BTLA interactions are dispensable for de novo host antidonor isotype-specific antibody formation after skin transplantation. PMID: 26924526
- Circulating BTLA+CD4+ lymphocytes are significantly increased in LPS-induced acute lung inflammation. PMID: 28164546
- Dendritic cells utilize BTLA and HVEM to modulate tolerizing T cell responses under steady-state conditions. PMID: 27793593
- CCR7 and BTLA co-expression in immature dendritic cells results in an intermediate immune phenotype compared to CCR7- or BTLA-expressing counterparts. PMID: 28393074
- miR-155 inhibits BTLA expression during CD4+ T cell activation. PMID: 27350630
- BTLA controls inflammatory responses by increasing Foxp3 expression in dextran sulfate sodium-induced colitis, rather than attenuating IL-17 production. PMID: 25973010
- BTLA allows Listeria proliferation, enhancing T cell responses for long-term protection. PMID: 25011109
- HVEM-triggered BTLA on innate leukocytes delivers negative signals, interfering with the protective immune response to intestinal parasites. PMID: 25595777
- BTLA, RORgammat, and IL-7 regulate gammadelta T cell homeostasis and inflammatory responses. PMID: 24315996
- BTLA enhances macrophage viability and function in virus-induced fulminant hepatitis, suggesting it as a therapeutic target. PMID: 22637698
- BTLA suppresses LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling. PMID: 23479601
- BTLA and HVEM are potential diagnostic markers for innate immune response and therapeutic targets for sepsis. PMID: 22459947
- Combined BTLA and HVEM blockade decreases alloreactive T cell activity in graft-versus-host reaction, without inhibiting donor T cell infiltration. PMID: 22490863
- During increased malaria resistance, BTLA regulates proinflammatory cytokine production (T cell-intrinsic), while B cells regulate nonlethal Plasmodium yoelii 17NL-specific antibody production. PMID: 21998455
- BTLA is a potential immunoregulatory target for modulating cytotoxic T-lymphocyte-mediated responses. PMID: 21978997
- BTLA acts both as a costimulatory ligand of HVEM and transmits inhibitory signals as a receptor in graft-versus-host disease (GVHD). PMID: 21220749
- BTLA's effect on CD4+ T cell-mediated corneal immunopathology during murine herpetic stromal keratitis was investigated. PMID: 21042564
- Targeting BTLA prevents graft-versus-host disease without global immunosuppression. PMID: 21078889
- BTLA suppresses IgG2a and IgG2b production by inhibiting IL-21 production from follicular T helper (Th) cells. PMID: 20660710
- The subcellular localization of BTLA in mouse T cells was examined under steady-state and activation conditions. PMID: 19892849
- BTLA extracellular domain binding to herpesvirus entry mediator (HVEM) blocks BTLA-HVEM interactions, improving antitumor immunity in cervical cancer when combined with HSP70 vaccine. PMID: 19923459
- BTLA is an inhibitory receptor on T lymphocytes, similar to CTLA-4 and PD-1. PMID: 12796776
- BTLA is expressed by mature lymphocytes, splenic macrophages, and mature dendritic cells, and acts as a negative regulator of hemopoietic cell activation/function. PMID: 15128774
- HVEM binding to BTLA attenuates T cell activation, identifying HVEM/BTLA as a coinhibitory receptor pair. PMID: 15647361
- Three distinct BTLA alleles exist among murine strains, differing in Ig domain structure and cellular expression. PMID: 15749870
- BTLA is a potential target for down-modulating T cell function. PMID: 16272294
- HVEM and BTLA are critical determinants of allergic airway inflammation duration. PMID: 16547224
- BTLA regulates B7 expression on dendritic cells. PMID: 16805995
- BTLA deficiency (or HVEM deficiency) leads to increased memory CD8(+) T cells. PMID: 17206146
- BTLA inhibits eosinophil recruitment by preventing IL-5 production from Th2 cells. PMID: 17541277
- BTLA regulates T-cell signaling by controlling phosphorylated TCRzeta accumulation in lipid rafts. PMID: 17607320
- HVEM-BTLA interactions regulate T cell regulation during Plasmodium berghei infection and T cell sequestration in brain capillaries. PMID: 17785848
- LTbetaR and HVEM-BTLA pathways form a signaling network regulating DC homeostasis. PMID: 18097025
- BTLA uses a conserved binding mode for HVEM recognition. PMID: 18178834
- HVEM triggers inhibitory signals by binding to BTLA. PMID: 18519647
- BTLA is important for immune tolerance and preventing autoimmune diseases. PMID: 18668554
- BTLA regulates T cell proliferation, recruitment, and survival in response to inhaled allergens. PMID: 18713967
- BTLA induces peripheral tolerance of CD4(+) and CD8(+) T cells. PMID: 19342624
- BTLA coinhibitory signaling in NKT cells tempers early inflammation in acute hepatitis. PMID: 19535622
- BTLA down-modulates immune responses. PMID: 19567411
- HVEM-BTLA interaction negatively regulates early immunity against intracellular bacteria. PMID: 19587015
- The HVEM-BTLA cis-complex inhibits HVEM activation, maintaining T cells in a naive state. PMID: 19915044
- BTLA functions as an inhibitory coreceptor of NKT cells. PMID: 19949073
