The role of the airway epithelium in the modulation of the immune response towards LPS in asthma

Asthma is a chronic lung disease, hereby patients have recurrent episodes of reversal airway obstruction. During these episodes patients suffer from shortness of breath, coughing and chest tightness. A T helper 2 (Th2) reaction to inhaled allergens is associated with asthma and allergy. Possibly, there is an imbalance between the T helper 1 (Th1), Th2, T helper 17 (Th17) and regulatory T cells (Treg) in asthmatic patients, with a shift towards a Th2 response. According to the hygiene hypothesis, frequent infection during childhood can prevent the development of asthma. Frequent bacterial challenge can possibly promote a shift towards the Th1 immune response. The first site of contact with an allergen is the airway epithelium. The airway epithelium is now seen as central player in the Th2 immune response by influencing the function of dendritic cells (DC). DC are professional antigen presenting cells (APC) that can activate naïve Th cells. Different cytokine signals released by airway epithelial cells can modulate and activate DC, DC then polarize naïve Th cells to become Th1, Th2 or Treg effector cells. Lipopolysaccharide (LPS), is a component of the cell wall of gram-negative bacteria. There are conflicting results about the role of LPS is asthma, it is not known whether LPS protect from the development of asthma or promotes the development of asthma. The dose of LPS may be an important factor, because different doses of LPS give different Th cell responses. The airway epithelium can bind LPS on their toll like receptors (TLR). This activates airway epithelial cells and induces the release of different cytokines. These cytokines can prime DC to induce Th cells polarization, towards either a Th1, Th2 or Treg immune response. In this essay, the central question is whether the airway epithelium releases different cytokines upon stimulation by different doses of LPS. A high dose of LPS could stimulate the release of Th1/Treg promoting cytokines, a low dose of LPS may stimulate the development of asthma by promoting the release of Th2 inducing cytokines by the epithelium.