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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Interleukin-17 is a negative regulator of established allergic asthma
Journal of Experimental Medicine, Volume 203, No. 12, Year 2006
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Description
T helper (Th)17 cells producing interleukin (IL)-17 play a role in autoimmune and allergic inflammation. Here, we show that IL-23 induces IL-17 in the lung and IL-17 is required during antigen sensitization to develop allergic asthma, as shown in IL-17R-deficient mice. Since IL-17 expression increased further upon antigen challenge, we addressed its function in the effector phase. Most strikingly, neutralization of IL-17 augmented the allergic response in sensitized mice. Conversely, exogenous IL-17 reduced pulmonary eosinophil recruitment and bronchial hyperreactivity, demonstrating a novel regulatory role of IL-17. Mechanistically, IL-17 down modulated eosinophil-chemokine eotaxin (CCL11) and thymus- and activation-regulated chemokine/CCL17 (TARC) in lungs in vivo and ex vivo upon antigen restimulation. In vitro, IL-17 reduced TARC production in dendritic cells (DCs) - the major source of TARC- and antigen uptake by DCs and IL-5 and IL-13 production in regional lymph nodes. Furthermore, IL-17 is regulated in an IL-4-dependent manner since mice deficient for IL-4Rα signaling showed a marked increase in IL-17 concentration with inhibited eosinophil recruitment. Therefore, endogenous IL-17 is controlled by IL-4 and has a dual role. Although it is essential during antigen sensitization to establish allergic asthma, in sensitized mice IL-17 attenuates the allergic response by inhibiting DCs and chemokine synthesis. JEM © The Rockefeller University Press.
Authors & Co-Authors
Schnyder-Candrian, Silvia
Unknown Affiliation
Togbé, Dieudonnée
Unknown Affiliation
Couillin, Isabelle
Unknown Affiliation
Mercier, Isabelle
Unknown Affiliation
Brombacher, Frank
Unknown Affiliation
Quesniaux, Valérie F.J.
Unknown Affiliation
Fossiez, Francois
Unknown Affiliation
Ryffel, Bernhard
Unknown Affiliation
Schnyder, Bruno
Unknown Affiliation
Statistics
Citations: 628
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1084/jem.20061401
ISSN:
00221007
e-ISSN:
00221007