CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection

Show full item record



Come , C , Cvrljevic , A , Khan , M M , Treise , I , Adler , T , Aguilar-Pimentel , J A , Au-Yeung , B , Sittig , E , Laajala , T D , Chen , Y , Oeder , S , Calzada-Wack , J , Horsch , M , Aittokallio , T , Busch , D H , Ollert , M W , Neff , F , Beckers , J , Gailus-Durner , V , Fuchs , H , de Angelis , M H , Chen , Z , Lahesmaa , R & Westermarck , J 2016 , ' CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection ' , PLoS One , vol. 11 , no. 4 , 0152996 .

Title: CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection
Author: Come, Christophe; Cvrljevic, Anna; Khan, Mohd Moin; Treise, Irina; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Au-Yeung, Byron; Sittig, Eleonora; Laajala, Teemu Daniel; Chen, Yiling; Oeder, Sebastian; Calzada-Wack, Julia; Horsch, Marion; Aittokallio, Tero; Busch, Dirk H.; Ollert, Markus W.; Neff, Frauke; Beckers, Johannes; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabe; Chen, Zhi; Lahesmaa, Riitta; Westermarck, Jukka
Contributor organization: Institute for Molecular Medicine Finland
Tero Aittokallio / Principal Investigator
Date: 2016-04-21
Language: eng
Number of pages: 18
Belongs to series: PLoS One
ISSN: 1932-6203
Abstract: 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.
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
asset.pdf 7.192Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record