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Title: IL-10- and IL-12-independent down-regulation of allergic sensitization by stimulation of CD40 signaling
Authors: Hellings, Peter ×
Kasran, Ahmad
Bullens, Dominique
Overbergh, Lutgart
Mathieu, Chantal
Heremans, Hubertine
Matthys, Patrick
Boon, Louis
Jorissen, Mark
Ceuppens, Jan #
Issue Date: Oct-2006
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:177 issue:8 pages:5138-5144
Abstract: Interaction between CD154 (CD40 ligand) on activated T lymphocytes and its receptor CD40 has been shown to be critically involved in the generation of cell-mediated as well as humoral immunity. CD40 triggering activates dendritic cells (DC), enhances their cytokine production, up-regulates the expression of costimulatory molecules, and induces their maturation. It is unknown how stimulation of CD40 during sensitization to an airborne allergen may affect the outcome of allergic airway inflammation. We took advantage of a mouse model of allergic asthma and a stimulatory mAb to CD40 (FGK45) to study the effects of CD40-mediated DC activation on sensitization to OVA and subsequent development of OVA-induced airway inflammation. Agonistic anti-CD40 mAb (FGK45) injected during sensitization with OVA abrogated the development of allergic airway inflammation upon repeated airway challenges with OVA. Inhibition of bronchial eosinophilia corresponded with reduced Th2 cytokine production and was independent of IL-12, as evidenced by a similar down-regulatory effect of anti-CD40 mAb in IL-12 p40-deficient mice. In addition, FGK45 equally down-regulated allergic airway inflammation in IL-10-deficient mice, indicating an IL-10-independent mechanism of action of FGK45. In conclusion, our results show that CD40 signaling during sensitization shifts the immune response away from Th2 cytokine production and suppresses allergic airway inflammation in an IL-12- and IL-10-independent way, presumably resulting from enhanced DC activation during sensitization.
URI: 
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Oto-rhino-laryngology
Laboratory of Clinical Immunology
Clinical and Experimental Endocrinology
Laboratory of Immunobiology (Rega Institute)
Laboratory of Pediatric Immunology
× corresponding author
# (joint) last author

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