Is there a regulatory role of immunoglobulins on tissue forming cells relevant in chronic inflammatory lung diseases?

Abstract

Epithelial cells, fibroblasts and smooth muscle cells together form and give structure to the airway wall. These three tissue forming cell types are structure giving elements and participate in the immune response to inhaled particles including allergens and dust. All three cell types actively contribute to the pathogenesis of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Tissue forming cells respond directly to allergens through activated immunoglobulins which then bind to their corresponding cell surface receptors. It was only recently reported that allergens and particles traffic through epithelial cells without modification and bind to the immunoglobulin receptors on the surface of sub-epithelial mesenchymal cells. In consequence, these cells secrete pro-inflammatory cytokines, thereby extending the local inflammation. Furthermore, activation of the immunoglobulin receptors can induce proliferation and tissue remodeling of the tissue forming cells. New studies using anti-IgE antibody therapy indicate that the inhibition of immunoglobulins reduces the response of tissue forming cells. The unmeasured questions are: (i) why do tissue forming cells express immunoglobulin receptors and (ii) do tissue forming cells process immunoglobulin receptor bound particles? The focus of this review is to provide an overview of the expression and function of various immunoglobulin receptors.

Figure 1

The network of interactions between tissue-forming resident airway cells and immune cells.

Figure 2

Epithelial cells express IgE and IgG receptors and respond directly to the respective immunoglobulins. Suggested (dashed line) and proven intracellular signaling pathways in human and animal airway epithelial cells. Importantly the IgG receptor expressed on airway epithelial cells may enable antigens to path un-changed through the epithelium and then contact with subepithelial mesenchymal cells [77].

Figure 3

Expression and function of immunoglobulins and their receptors on human airway smooth muscle cells. Likely interaction and crosstalk of Ig receptors through shared intracellular signaling pathways. Reported pathways by which Ig receptors modulate cytokine synthesis by tissue-forming cells in chronic inflammatory lung diseases.