Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/36338
Title: Mycobacterium tuberculosis infection induces il12rb1 splicing to generate a novel IL-12Rbeta1 isoform that enhances DC migration
Authors: Robinson, R. T.
Khader, S. A.
Martino, C. A.
Fountain, J. J.
Teixeira-Coelho, M.
Pearl, John Edward
Smiley, S. T.
Winslow, G. M.
Woodland, D. L.
Walter, M. J.
Conejo-Garcia, J. R.
Gubler, U.
Cooper, A. M.
First Published: 15-Mar-2010
Publisher: Rockefeller University Press
Citation: Journal of Experimental Medicine, 2010, 207 (3), pp. 591-605
Abstract: RNA splicing is an increasingly recognized regulator of immunity. Here, we demonstrate that after Mycobacterium tuberculosis infection (mRNA) il12rb1 is spliced by dendritic cells (DCs) to form an alternative (mRNA) il12rb1Deltatm that encodes the protein IL-12Rbeta1DeltaTM. Compared with IL-12Rbeta1, IL-12Rbeta1DeltaTM contains an altered C-terminal sequence and lacks a transmembrane domain. Expression of IL-12Rbeta1DeltaTM occurs in CD11c(+) cells in the lungs during M. tuberculosis infection. Selective reconstitution of il12rb1(-/-) DCs with (mRNA) il12rb1 and/or (mRNA) il12rb1Deltatm demonstrates that IL-12Rbeta1DeltaTM augments IL-12Rbeta1-dependent DC migration and activation of M. tuberculosis-specific T cells. It cannot mediate these activities independently of IL12Rbeta1. We hypothesize that M. tuberculosis-exposed DCs express IL-12Rbeta1DeltaTM to enhance IL-12Rbeta1-dependent migration and promote M. tuberculosis-specific T cell activation. IL-12Rbeta1DeltaTM thus represents a novel positive-regulator of IL12Rbeta1-dependent DC function and of the immune response to M. tuberculosis.
DOI Link: 10.1084/jem.20091085
ISSN: 0022-1007
eISSN: 1540-9538
Links: http://jem.rupress.org/content/207/3/591
http://hdl.handle.net/2381/36338
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2010 Robinson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation



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