Datasheet

生物学的記述

Specificity	DR3 Antibody (Rabbit mAb) [B17K2] detects endogenous levels of total DR3 proteins.
Background	Gene-targeted mice lacking DR3 were used to show that exogenous TL1A costimulates T-cell proliferation and cytokine production in wild-type but not DR3-deficient T cells, directly confirming DR3 as the nonredundant receptor for TL1A-induced costimulation; DR3-deficient T cells only displayed defects when activated in the presence of dendritic cells, establishing dendritic cells rather than T cells themselves as the physiologically relevant source of TL1A. In the same study, DR3-deficient mice underwent normal T-cell priming and polarized normally into Th1, Th2 and Th17 subsets both in vitro and in vivo, and controlled Toxoplasma gondii infection as effectively as wild-type mice, showing that DR3 is dispensable for initial activation and differentiation; DR3 was instead required specifically for T-cell accumulation, cytokine production and tissue immunopathology in disease models including experimental autoimmune encephalomyelitis and allergic lung inflammation, indicating that DR3 acts selectively at the effector phase of established responses in inflamed tissue. Mechanistically, binding of TL1A to the cytoplasmic death domain of DR3 recruits the adaptor TRADD together with RIPK1 and TRAF2, and RIPK1 undergoes cIAP1/2-mediated K63-linked polyubiquitination that creates a docking platform for TAK1 and the IKK complex of IKKα, IKKβ and NEMO; recruitment of the linear ubiquitin chain assembly complex to this platform further reinforces activation of the JNK, p38 and ERK MAP kinase cascades together with canonical NF-κB signaling. Pharmacological blockade of NF-κB, but not of the MAP kinase cascades, converts DR3 signaling from a survival-promoting into a cell death-inducing pathway, showing that ongoing NF-κB-dependent transcription of antiapoptotic genes normally suppresses a latent apoptotic output of the same receptor-proximal complex. Adoptive transfer experiments using dominant-negative DR3 transgenic natural killer T cells restored resistance to allergic lung inflammation in NKT-cell-deficient mice, demonstrating that DR3 signaling specifically within this lymphocyte subset drives this particular disease phenotype.

Specificity

DR3 Antibody (Rabbit mAb) [B17K2] detects endogenous levels of total DR3 proteins.

Background

Gene-targeted mice lacking DR3 were used to show that exogenous TL1A costimulates T-cell proliferation and cytokine production in wild-type but not DR3-deficient T cells, directly confirming DR3 as the nonredundant receptor for TL1A-induced costimulation; DR3-deficient T cells only displayed defects when activated in the presence of dendritic cells, establishing dendritic cells rather than T cells themselves as the physiologically relevant source of TL1A. In the same study, DR3-deficient mice underwent normal T-cell priming and polarized normally into Th1, Th2 and Th17 subsets both in vitro and in vivo, and controlled Toxoplasma gondii infection as effectively as wild-type mice, showing that DR3 is dispensable for initial activation and differentiation; DR3 was instead required specifically for T-cell accumulation, cytokine production and tissue immunopathology in disease models including experimental autoimmune encephalomyelitis and allergic lung inflammation, indicating that DR3 acts selectively at the effector phase of established responses in inflamed tissue. Mechanistically, binding of TL1A to the cytoplasmic death domain of DR3 recruits the adaptor TRADD together with RIPK1 and TRAF2, and RIPK1 undergoes cIAP1/2-mediated K63-linked polyubiquitination that creates a docking platform for TAK1 and the IKK complex of IKKα, IKKβ and NEMO; recruitment of the linear ubiquitin chain assembly complex to this platform further reinforces activation of the JNK, p38 and ERK MAP kinase cascades together with canonical NF-κB signaling. Pharmacological blockade of NF-κB, but not of the MAP kinase cascades, converts DR3 signaling from a survival-promoting into a cell death-inducing pathway, showing that ongoing NF-κB-dependent transcription of antiapoptotic genes normally suppresses a latent apoptotic output of the same receptor-proximal complex. Adoptive transfer experiments using dominant-negative DR3 transgenic natural killer T cells restored resistance to allergic lung inflammation in NKT-cell-deficient mice, demonstrating that DR3 signaling specifically within this lymphocyte subset drives this particular disease phenotype.

使用情報

Application

WB, IP

Dilution

WB	IP
1:1000	1:100

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

45 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/18571443/
https://pubmed.ncbi.nlm.nih.gov/28686297/

DR3 Antibody (Rabbit mAb) [B17K2]

生物学的記述

使用情報

References

Application Data