TY - JOUR
T1 - CIP2A promotes T-cell activation and immune response to Listeria monocytogenes infection
AU - Côme, Christophe
AU - Cvrljevic, Anna
AU - Khan, Mohd Moin
AU - Treise, Irina
AU - Adler, Thure
AU - Aguilar-Pimentel, Juan Antonio
AU - Au-Yeung, Byron
AU - Sittig, Eleonora
AU - Laajala, Teemu Daniel
AU - Chen, Yiling
AU - Oeder, Sebastian
AU - Calzada-Wack, Julia
AU - Horsch, Marion
AU - Aittokallio, Tero
AU - Busch, Dirk H.
AU - Ollert, Markus W.
AU - Neff, Frauke
AU - Beckers, Johannes
AU - Gailus-Durner, Valerie
AU - Fuchs, Helmut
AU - De Angelis, Martin Hrabì
AU - Chen, Zhi
AU - Lahesmaa, Riitta
AU - Westermarck, Jukka
N1 - Publisher Copyright:
© 2016 Côme et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/4
Y1 - 2016/4
N2 - 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 (CIP2AHOZ) present a normal immune system development and function in unchallenged conditions. However when challenged with Listeria monocytogenes, CIP2AHOZ 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 CIP2AHOZ 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.
AB - 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 (CIP2AHOZ) present a normal immune system development and function in unchallenged conditions. However when challenged with Listeria monocytogenes, CIP2AHOZ 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 CIP2AHOZ 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.
UR - http://www.scopus.com/inward/record.url?scp=84964626208&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0152996
DO - 10.1371/journal.pone.0152996
M3 - Article
C2 - 27100879
AN - SCOPUS:84964626208
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0152996
ER -