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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3762-3771. Prepublished online as a Blood First Edition Paper on May 21, 2008; DOI 10.1182/blood-2008-01-135251. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-01-135251v1 112/9/3762    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Spiegl, N. Articles by Dahinden, C. A. Search for Related Content PubMed PubMed Citation Articles by Spiegl, N. Articles by Dahinden, C. A. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human basophils activated by mast cell–derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid Nicole Spiegl1, Svetlana Didichenko1, Peter McCaffery2, Hanno Langen3, and Clemens A. Dahinden1 1 Institute of Immunology, University Hospital Bern, Inselspital, Bern, Switzerland; 2 Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom; and 3 Proteomics Initiative, Roche Center for Medical Genomics, Basel, Switzerland The vitamin A metabolite retinoic acid (RA) plays a fundamental role in cellular functions by activating nuclear receptors. Retinaldehyde dehydrogenase-II (RALDH2) creates localized RA gradients needed for proper embryonic development, but very little is known regarding its regulated expression in adults. Using a human ex vivo model of aller-gic inflammation by coincubating IgE receptor–activated mast cells (MCs) with blood basophils, we observed prominent induction of a protein that was identified as RALDH2 by mass spectroscopy. RALDH2 was selectively induced in basophils by MC-derived interleukin-3 (IL-3) involving PI3-kinase and NF-B pathways. Importantly, neither constitutive nor inducible RALDH2 expression was detectable in any other human myeloid or lymphoid leukocyte, including dendritic cells. RA generated by RALDH2 in basophils modulates IL-3–induced gene expression in an autocrine manner, providing positive (CD25) as well as negative (granzyme B) regulation. It also acts in a paracrine fashion on T-helper cells promoting the expression of CD38 and 4/β7 integrins. Furthermore, RA derived from IL-3–activated basophils provides a novel mechanism of Th2 polarization. Thus, RA must be viewed as a tightly controlled basophil-derived mediator with a high potential for regulating diverse functions of immune and resident cells in allergic diseases and other Th2-type immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: "Vitamin hypothesis": explanation for allergy increase? Stephan C. Bischoff Blood 2008 112: 3535-3536. [Full Text] [PDF] This article has been cited by other articles: E. Kuroda, V. Ho, J. Ruschmann, F. Antignano, M. Hamilton, M. J. Rauh, A. Antov, R. A. Flavell, L. M. Sly, and G. Krystal SHIP Represses the Generation of IL-3-Induced M2 Macrophages by Inhibiting IL-4 Production from Basophils J. Immunol., September 15, 2009; 183(6): 3652 - 3660. [Abstract] [Full Text] [PDF] T. Pecaric-Petkovic, S. A. Didichenko, S. Kaempfer, N. Spiegl, and C. A. Dahinden Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 Blood, February 12, 2009; 113(7): 1526 - 1534. [Abstract] [Full Text] [PDF]

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