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Blood, 5 February 2009, Vol. 113, No. 6, pp. 1268-1277. Prepublished online as a Blood First Edition Paper on October 22, 2008; DOI 10.1182/blood-2008-07-166553. This Article Full Text (PDF) All Versions of this Article: blood-2008-07-166553v1 113/6/1268    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tahvanainen, J. Articles by Lahesmaa, R. Search for Related Content PubMed PubMed Citation Articles by Tahvanainen, J. Articles by Lahesmaa, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 3, 2008 Accepted September 28, 2008 PRELI is a mitochondrial regulator of human primary T helper cell apoptosis, STAT6 and Th2 cell differentiation Johanna Tahvanainen, Teemu Kallonen, Hanna Lahteenmaki, Kaisa M Heiskanen, Jukka Westermarck, Kanury V.S. Rao, and Riitta Lahesmaa* Drug Discovery Graduate School, University of Turku, Turku, Finland Department of Bacterial and Inflammatory Diseases, National Public Health Institute, Turku, Finland Department of Biology, University of Oulu, Oulu, Finland Department of Biology, University of Turku, Turku, Finland Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland International Centre for Genetic Engineering and Biotechnology, New Delhi, India Turku Centre for Biotechnology, University of Turku and Abo Akademi, Turku, Finland * Corresponding author; email: riitta.lahesmaa{at}btk.fi. The identification of novel factors regulating human T helper (Th) cell differentiation into functionally distinct Th1 and Th2 subsets is important for understanding the mechanisms behind human autoimmune and allergic diseases. We have identified PRELI, a novel protein that induces oxidative stress and mitochondrial apoptosis pathway in human primary Th cells. We also demonstrate that PRELI inhibits Th2 cell development and downregulates STAT6, a key transcription factor driving Th2 differentiation. Our data suggest that Calpain, an oxidative stress induced cysteine protease, is involved in the PRELI-induced downregulation of STAT6. Moreover, we observed that a strong T cell receptor (TCR) stimulus induces expression of PRELI and inhibits Th2 development. Our results suggest that PRELI is involved in a mechanism wherein the strength of the TCR stimulus influences the polarization of Th cells. This study identifies PRELI as a novel factor influencing the human primary Th cell death and differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Tamura, T. Endo, M. Iijima, and H. Sesaki Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria J. Cell Biol., June 15, 2009; 185(6): 1029 - 1045. [Abstract] [Full Text] [PDF]

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