A1 Refereed original research article in a scientific journal
CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection
Authors: Côme C, Cvrljevic A, Khan MM, Treise I, Adler T, Aguilar-Pimentel JA, Au-Yeung B, Sittig E, Laajala TD, Chen Y, Oeder S, Calzada-Wack J, Horsch M, Aittokallio T, Busch DH, Ollert MW, Neff F, Beckers J, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Chen Z, Lahesmaa R, Westermarck J
Publication year: 2016
Journal: PLoS ONE
Article number: e0152996
Volume: 11
Issue: 4
Number of pages: 18
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0152996(external)
The
oncoprotein Cancerous Inhibitor of Protein Phosphatase 2A ( CIP2A) is
overexpressed in most malignancies and is an obvious candidate target
protein for future cancer therapies. However, the physiological
importance of CIP2A-mediated PP2A inhibition is largely unknown. As PP2A
regulates immune responses, we investigated the role of CIP2A in normal
immune system development and during immune response in vivo. We show
that CIP2A-deficient mice (CIP2A(HOZ)) present a normal immune system
development and function in unchallenged conditions. However when
challenged with Listeria monocytogenes, CIP2A(HOZ) mice display an
impaired adaptive immune response that is combined with decreased
frequency of both CD4(+) T-cells and CD8(+) effector T-cells.
Importantly, the cell autonomous effect of CIP2A deficiency for T-cell
activation was confirmed. Induction of CIP2A expression during T-cell
activation was dependent on Zap70 activity. Thus, we reveal CIP2A as a
hitherto unrecognized mediator of T-cell activation during adaptive
immune response. These results also reveal CIP2A(HOZ) as a possible
novel mouse model for studying the role of PP2A activity in immune
regulation. On the other hand, the results also indicate that CIP2A
targeting cancer therapies would not cause serious immunological
side-effects.
