Granulin Is a Soluble Cofactor for Toll-like Receptor 9 Signaling
Name
Park-2011-Granulin Is a Solubl.pdf
Size
910.02 KB
Format
Adobe PDF
Checksum (MD5)
21b1b72680be0b07d15269d603a33e86
Author(s)
Park, Boyoun
Buti, Ludovico
Lee, Sungwook
Matsuwaki, Takashi
Spooner, Eric
Brinkmann, Melanie M.
Nishihara, Masugi
Ploegh, Hidde
Date Issued
April 2011
Journal
Immunity
Publisher
Elsevier
Citation
Park, Boyoun, Ludovico Buti, Sungwook Lee, Takashi Matsuwaki, Eric Spooner, Melanie M. Brinkmann, Masugi Nishihara, and Hidde L. Ploegh. “Granulin Is a Soluble Cofactor for Toll-Like Receptor 9 Signaling.” Immunity 34, no. 4 (April 2011): 505–513. © 2011 Elsevier Inc.
Version
Final published version
Abstract
Toll-like receptor (TLR) signaling plays a critical role in innate and adaptive immune responses and must be tightly controlled. TLR4 uses LPS binding protein, MD-2, and CD14 as accessories to respond to LPS. We therefore investigated the presence of an analagous soluble cofactor that might assist in the recruitment of CpG oligonucleotides (CpG-ODNs) to TLR9. We report the identification of granulin as an essential secreted cofactor that potentiates TLR9-driven responses to CpG-ODNs. Granulin, an unusual cysteine-rich protein, bound to CpG-ODNs and interacted with TLR9. Macrophages from granulin-deficient mice showed not only impaired delivery of CpG-ODNs to endolysosomal compartments, but also decreased interaction of TLR9 with CpG-ODNs. As a consequence, granulin-deficient macrophages showed reduced responses to stimulation with CpG-ODNs, a trait corrected by provision of exogenous granulin. Thus, we propose that granulin contributes to innate immunity as a critical soluble cofactor for TLR9 signaling.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.immuni.2011.01.018
