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Modulation de la réponse immunitaire par TLR7: rôle dans le diabète de type 1 et l'asthme allergique.

Abstract : According to hygiene hypothesis, infections can protect from immune disorders such as autoimmune and allergic diseases. We have demonstrated that stimulation of TLRs that are implicated in sensing infections, can protect from type 1 diabetes. Indeed we show that treatment of NOD mice, which develop a spontaneous diabetes, with TLR2, 3, 4 and 7 agonists protect animals from disease onset. Even if all these structures exert a protective effect, protective mechanisms are specific for each receptor. TLR stimulation activates regulatory cells and immunoregulatory cytokines. We have further demonstrated that TLR2- and TLR3-induced protection were dependent on iNKT cells with an implication of IL-4 for TLR3. In an allergic asthma model, we have shown that TLR7-induced protection was dependent on iNKT cells and IFN-γ. In order to understand mechanisms underlining TLR-iNKT cell triggering, we have performed in vitro analyses and observed that TLR7 agonist directly targeted iNKT cells without requirement of antigen presenting cells. Taken together, our work emphasize the modulatory role of TLR signaling pathways in immune responses, and especially those due to a rupture of tolerance like in immune disorders.
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Contributor : Catherine Slama <>
Submitted on : Wednesday, September 17, 2008 - 2:31:52 PM
Last modification on : Friday, October 23, 2020 - 4:35:33 PM


  • HAL Id : tel-00322355, version 1



Françoise Grela. Modulation de la réponse immunitaire par TLR7: rôle dans le diabète de type 1 et l'asthme allergique.. Sciences du Vivant [q-bio]. Université René Descartes - Paris V, 2008. Français. ⟨tel-00322355⟩



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