The Journal of Experimental Medicine
Translational Medicine Lupus Symposium
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Published online January 14, 2008
doi:10.1084/jem.20062027
The Journal of Experimental Medicine, Vol. 205, No. 1, 79-90
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Yang et al.
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ARTICLE

 Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses

De Yang1,2, Qian Chen2, Shao Bo Su3, Ping Zhang5, Kahori Kurosaka2, Rachel R. Caspi3, Suzanne M. Michalek5, Helene F. Rosenberg4, Ning Zhang2,6, and Joost J. Oppenheim2

1 Basic Research Program, SAIC-Frederick, Inc., and 2 Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702
3 Laboratory of Immunology, National Eye Institute, and 4 Eosinophil Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892
5 Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294
6 Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

CORRESPONDENCE De Yang: dyang{at}ncifcrf.gov OR Joost J. Oppenheim: oppenhei{at}ncifcrf.gov

Eosinophil-derived neurotoxin (EDN) is an eosinophil granule–derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2–myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specific T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specific interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen-specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen-specific Th2 immune responses.

Abbreviations used: AMP, antimicrobial peptide or protein; EDN, eosinophil-derived neurotoxin; FSL, fibroblast-stimulating lipopeptide; hAng, human angiogenin; HMGB1, high mobility group box 1; HPC, hematopoietic progenitor cell; iDC, immature DC; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation factor 88; PGN, peptidoglycan; RANTES, regulated upon activation, normal T cell–expressed, and secreted; RLU, relative luciferase unit; SDF, stromal cell–derived factor; SLC, secondary lymphoid tissue chemokine; TLR, Toll-like receptor.


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