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Interactions entre épithélium bronchique et cellules dendritiques : implication de molécules membranaires

Abstract : Epidemiologic studies showed a correlation between atmospheric pollution and the frequency of respiratory diseases like asthma. The effects on health are partly due to diesel exhaust particles (DEP). However, the mechanisms by which DEP affect the immune system in respiratory tract is not completely understood.
Airway mucosa has to defend itself against pollutants or micro-organisms thanks to an immunological network of dendritic cells (DC) localized into the epithelium. DC play a key role in the development and the control of the immune and inflammatory response. DC are able to recognize self from non-self or modified self thanks to Pattern Recognition Receptors (PRR) (including Toll-like Receptors also called TLR, Scaveger Receptors also called SR) that recognize Pathogen-Associated Molecular Pattern (PAMP). Interestingly, SR are also implicated in inhaled inert particles recognition.
The aim of the work is to study the effect DEP and/or PAMP on the interactions between bronchial epithelium and DC. We particularly focused on the implication of membrane molecules such as ICAM-1, intercellular junction proteins and SR.
KpOmpA, the outer membrane protein A of Klebsiella pneumoniae, activates macrophages and DC, and possess immunomodulatory properties. The aim of the work was to study the crosstalk between bronchial epithelial cells (BEC) and DC after exposure to KpOmpA and the consequences on T cell response. Our results showed KpOmpA-exposed BEC induced the recruitment and the subsequent maturation of myeloid DC by a mechanism depending on ICAM-1. These DC induce the development of a Th2 response. These data show that BEC participate in the homeostasis of myeloid DC network and regulate the induction of local immune response by favouring the transition between innate and adaptive immunity.
In intestinal mucosa, the expression of intercellular junction proteins on DC allow these cells to send dendrites between intestinal epithelial cells and to capture bacteria without disrupting the barrier integrity. In this context, we supposed that this mechanism would allow antigen capture in bronchial lumen and impact on DC functions and. Our results showed that DC express adherens junction proteins E-Cadherin and β-Catenin and tight junction proteins ZO-1 and Occludin at steady state. TLR ligands modulate the expression of these proteins at mRNA and protein levels. Moreover, we showed for the first time that E-Cadherin probably modulates DC maturation during the establishment of intercellular junctions between BEC and DC.
Concerning SR, TLR ligands modulate SR expression at mRNA and protein levels contrary to the weak effect of DEP. Associated to TLR ligands, DEP modulate the action of TLR on SR expression. The pretreatment with SR agonists maleylated ovalbumin and dextran sulfate only inhibits the effects of the low dose DEP (1µg/ml) on DC maturation and cytokine secretion. SR ligands have any effect on DC maturation, cytokine or ROS production when DC are exposed to a high dose DEP (10µg/ml). These data suggest a participation for SR in DC interactions with DEP.
In conclusion, these data suggest the importance of adhesion molecules ICAM-1 or intercellular junction proteins and SR in mucosal DC immune response to PAMP and DEP. Our results also confirmed the interactions between both stimuli
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https://tel.archives-ouvertes.fr/tel-00373159
Contributor : Solenne Taront <>
Submitted on : Friday, April 3, 2009 - 2:55:57 PM
Last modification on : Thursday, February 21, 2019 - 9:56:02 AM
Long-term archiving on: : Thursday, June 10, 2010 - 7:41:13 PM

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Solenne Taront. Interactions entre épithélium bronchique et cellules dendritiques : implication de molécules membranaires. Immunologie. Université du Droit et de la Santé - Lille II, 2008. Français. ⟨tel-00373159⟩

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