Blocking the ART2.2/P2X7-system is essential to avoid a detrimental bias in functional CD4 T cell studies
Hristo Georgiev1, Inga Ravens1, Georgia Papadogianni1
1Institute of Immunology, Hannover Medical School, Hannover, Germany.
European Journal of Immunology
|March 7, 2018
Abstract:
Murine T cell subsets differ in their expression level of P2X7. Depending on several parameters like extracellular NAD+ , P2X7 can be ADP-ribosylated rapidly by adjacent ARTC2.2 resulting in susceptibilities to apoptosis to a varying extent. This detrimental effect can be prevented when drugs like KN-62 are present during cell preparations.
Insights
Murine T cell subsets exhibit varying P2X7 receptor expression. Extracellular NAD+ triggers ARTC2.2-mediated ADP-ribosylation, increasing apoptosis susceptibility, which KN-62 can prevent.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Murine T cell subsets display differential expression of the P2X7 receptor.
- The P2X7 receptor plays a role in cellular responses and apoptosis.
- Extracellular nucleotide metabolism influences immune cell function.
Purpose of the Study:
- To investigate the regulation of P2X7 receptor function in murine T cells.
- To elucidate the role of ADP-ribosylation in P2X7-mediated apoptosis.
- To identify potential modulators of P2X7-induced cell death.
Main Methods:
- Flow cytometry to assess P2X7 expression on murine T cell subsets.
- Biochemical assays to detect ADP-ribosylation of P2X7.
- Induction of apoptosis and assessment of cell viability.
- Pharmacological inhibition using KN-62.
Main Results:
- P2X7 expression levels varied significantly across different murine T cell subsets.
- Extracellular NAD+ levels correlated with rapid ADP-ribosylation of P2X7 by ARTC2.2.
- ADP-ribosylation led to increased susceptibility to apoptosis in a subset-dependent manner.
- The drug KN-62 effectively prevented P2X7-mediated apoptosis during cell preparation.
Conclusions:
- T cell subset-specific P2X7 expression influences apoptotic responses.
- ARTC2.2-mediated ADP-ribosylation is a key regulatory mechanism for P2X7 function.
- Pharmacological intervention with KN-62 can mitigate P2X7-induced cell death in experimental settings.
More Related Videos
Related Concept Videos
01:25Compounds Essential to Human Function
10.5K
The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all physiological processes in the body and are broadly classified into organic and inorganic based on their chemical structures.
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
10.5K
01:29Bias in Epidemiological Studies
1.4K
Biases can arise at various stages of research, from study design and data collection to analysis and interpretation. Recognizing and addressing these biases is essential to ensure the validity and reliability of epidemiological findings.Broadly speaking, biases in epidemiology fall into three main categories: selection bias, information bias, and confounding. A more detailed description of possible biases is:
1.4K
01:31Confirmation Biases
8.3K
The confirmation bias is the tendency to focus on information that confirms our existing beliefs and ignore information that is inconsistent with our expectations. For example, if you think that your professor is not very nice, you notice all of the instances of rude behavior exhibited by the professor while ignoring the countless pleasant interactions he is involved in on a daily basis. Have you ever fallen prey to the confirmation bias, either as the source or target of such bias?
8.3K
01:12Hindsight Biases
4.3K
Hindsight bias leads you to believe that the event you just experienced was predictable, even though it really wasn’t. In other words, you knew all along that things would turn out the way they did. Can you relate this to the phrase "Hindsight is 20/20" now?
4.3K
01:14Frustration and Conflict: Avoidance-Avoidance, Double-Approach Avoidance
698
Avoidance-avoidance conflict refers to a psychological situation where a person must choose between two or more unpleasant alternatives. These conflicts are particularly stressful because neither option is desirable. This dilemma is often expressed in sayings like "caught between a rock and a hard place" or "between the devil and the deep blue sea." For instance, individuals who fear dental procedures may find themselves torn between enduring a painful toothache or facing the...
698
01:22Bias
7.4K
Bias refers to any tendency that prevents a question from being considered unprejudiced. In research, bias occurs when one outcome or answer is selected or encouraged over others in sampling or testing. Bias can occur during any research phase, including study design, data collection, analysis, and publication.
In statistics, a sampling bias is created when a sample is collected from a population, and some members of the population are not as likely to be chosen as others (remember, each member...
In statistics, a sampling bias is created when a sample is collected from a population, and some members of the population are not as likely to be chosen as others (remember, each member...
7.4K