Dendritic cell-CD4+ T cell interaction: The differential role of IL-4/IL-13 in serum IgE levels in house dust mite allergic patients

Abstract

Allergic asthma is a chronic airway inflammatory disorder triggered by inhalant allergens. Interleukin (IL)-4 and IL-13 play a main role in the generation of T helper cell type 2 (Th2) immune response, induction of immunoglobulin E (IgE) synthesis and persistence of airway inflammation. The aim of the present study was to investigate the influence of Dermatophagoides pteronyssinus allergen Der p 1, the major allergen of house dust mite, on the synthesis of IL-4 and IL-13 by monocyte-derived dendritic cells (DCs) and naive CD4⁺ T cells cocultured with DCs, as well as their role in the production of serum IgE, in house dust mite (HDM) allergic patients. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients allergic to HDM and healthy donors and incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 to generate immature DCs. The obtained cells were stimulated for 24 h with Der p 1 to induce DC maturation, washed, and afterwards cocultured for 24 h with autologous naive CD4⁺ T cells. Culture supernatants were harvested for IL-4, IL-13 and IFN-γ level measurements. DCs stimulation with Der p 1 induced higher synthesis of IL-4 and IL-13 in HDM allergic patients, compared to healthy donors. The allergic group showed significant correlation between IL-13 production by Der p 1-pulsed DCs, and total serum IgE and IL-4 production of the same cells and Der p-specific IgE. To conclude, IL-4 and IL-13 are critically related to the regulation of serum IgE production in patients with allergic asthma. The relevance of these two cytokines in the pathophysiology of Th2 asthma endotype makes them an appropriate target in its management.

Keywords: CD4+ T cells; Ig E; allergic asthma; dendritic cells; interleukin-13; interleukin-4.

Figure 1

Serum cytokine (IL-4, IL-13 and IFN-γ) levels in allergic patients (APs) and healthy donors (HDs). IL, interleukin; IFN, interferon.

Figure 2

Correlation between cytokine (IL-4, IL-13 and IFN-γ) synthesis by stimulated-DCs and total or Der p-specific IgE in the AP group. AP, allergic patient; IL, interleukin; IFN, interferon; DCs, dendritic cells; IgE, immunoglobulin E.

Figure 3

Correlation between cytokine (IL-4, IL-13 and IFN-γ) synthesis by autologous T cells and total or Der p-specific IgE in the AP group. AP, allergic patient; IL, interleukin; IFN, interferon; IgE, immunoglobulin E.