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Pathological role of IL-6 in the experimental allergic bronchial asthma in mice

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Abstract

Although allergic asthma was described to be associated with the presence of mucosal T-helper (Th)2 cells, it is not entirely clear which factors are responsible for priming of T cells to differentiate into Th2 effector cells in this disease. Interleukin (IL)-6 has been recognized as important because it is secreted by cells of the innate immunity and induces the expansion of the Th2 effector cells, which are major players of the adaptive immune responses. Additionally, IL-6 released by dendritic cells (DCs) inhibits the suppressive function of CD4+CD25+ T-regulatory cells, thus inhibiting the peripheral tolerance. The signal transduction of IL-6 has recently taught us how this cytokine influences different aspects of the immune response, especially under pathological conditions. IL-6 can bind to the soluble IL-6R, increased after allergen challenge in asthmatic patients, and, through a mechanism called trans-signaling, induces proliferation of cells expressing the cognate receptor gp130. This mechanism appears to be used for proliferation by developed Th2 cells in the airways. In contrast, through the membrane-bound IL-6R, IL-6 controls CD4+CD25+ survival, as well as the initial stages of the Th2 cells development in the lung. These findings impact the establishment of new therapies for allergic diseases; indeed, blockade of the soluble IL-6R through the fusion protein gp130Fc reduces Th2 cells in the lung, and by blocking the membrane-bound Il-6R, anti-IL-6R antibody treatment induces the number of T-regulatory cells in the lung, thereby reducing the local number of CD4+ T-effector cells in experimental asthma.

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  1. Laboratory of Cellular and Molecular Immunology of the Lung, I. Medical Clinic, University of Mainz, Germany

    Aysefa Doganci, Kerstin Sauer, Roman Karwot & Susetta Finotto

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  1. Aysefa Doganci
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Correspondence to Susetta Finotto.

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Doganci, A., Sauer, K., Karwot, R. et al. Pathological role of IL-6 in the experimental allergic bronchial asthma in mice. Clinic Rev Allerg Immunol 28, 257–269 (2005). https://doi.org/10.1385/CRIAI:28:3:257

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