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CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival
Carlos A Mier-Aguilar1, Kevin S Cashman2, Chander Raman2,3
1Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México.
Plos One
|December 29, 2016
Summary
The CD5-CK2 signaling pathway is crucial for thymic selection, regulating T-cell survival and positive selection by modulating ERK activation, independent of initial T-cell receptor signals.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Signaling
Background:
- CD5 plays a key role in thymic selection, primarily through its ITIM domain.
- The mechanism of CD5's role in thymic selection is not fully understood.
- A CK2 binding/activation domain (CD5-CK2BD) in CD5's cytoplasmic tail is a potential regulatory element.
Purpose of the Study:
- To investigate the role of the CD5-CK2BD in thymic selection.
- To elucidate the signaling mechanisms by which CD5 regulates T-cell development.
Main Methods:
- Utilized gene-targeted mice lacking the CD5-CK2BD (CD5-ΔCK2BD).
- Employed TCR transgenic (OT-II) mice to study thymic selection.
- Analyzed thymocyte populations, apoptosis, ERK activation, nuclear localization, and calcium mobilization.
Main Results:
- Loss of CD5-CK2 signaling decreased double positive (DP) thymocytes and increased apoptosis.
- CD5-ΔCK2BD mice showed increased DP cells with high CD5/CD69 and increased CD4+SP thymocytes, indicating enhanced positive selection and survival.
- ERK activation and nuclear localization were elevated in thymic populations from CD5-ΔCK2BD mice.
- Calcium mobilization, an early TCR activation event, was unaffected by the loss of CD5-CK2 signaling.
Conclusions:
- The CD5-CK2 signaling axis is essential for regulating positive selection in the thymus.
- CD5-CK2 signaling promotes thymocyte survival by modulating ERK activation.
- This regulation occurs independently of proximal T-cell receptor (TCR) signaling events.
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