Blocking IL-20 pathway limits the development of bacteria induced exacerbation in mice chronically exposed to cigarette smoke.

COPD is a public health burden mainly due to cigarette smoking (CS). It is now well recognized that respiratory infections are important triggers for the progression and exacerbation of the disease, consecutive to a defective immune responses. Since IL-20 cytokines (IL-19, IL-20 and IL-24) inhibits cutaneous antibacterial responses, we evaluated their implication during COPD exacerbation in order to restore an efficient immune response.C57BL/6 mice were daily exposed to CS during 12 weeks before infection by Streptococcus pneumoniae (Sp). Moreover, human monocyte-derived dendritic cells (MDDC) were treated with IL-20 cytokines during Sp-induced maturation. Expression of IL-20 cytokines and their receptors was evaluated. The role of IL-20 cytokines was assessed in vivo and in vitro using IL-20RB receptor blocking mAbs.CS exposure and Sp challenge increased IL-20 cytokines in vivo and in vitro in MDDC. Treatment with anti-IL-20RB mAb strongly reduced bacterial burden and inflammatory responses in Sp infected CS-exposed mice. It also modulated DC number and activation. MDDC expressed IL-20 receptor IL-20Ra, IL-20Rb and IL22Ra. Incubation with IL-20 cytokines inhibited Sp-induced MDDC maturation as shown by polarizing cytokines (IL-1β, IL-6, IL-23) as well as their capacity to activate naive T lymphocytes. Addition of IL-20RB blocking mAbs before cytokine treatment restores MDDC maturation and function.We show that IL-20 cytokines inhibit antibacterial responses in CS-mice p...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway Cell Biology and Immunopathology Source Type: research