Epithelial cells
There are many environmental and cellular components that affect DC behaviour but one particularly important in allergy is the interaction with epithelial cells.
The epithelium, whether lining the airways, skin or GI tract, provides a chemical, physical and immunological barrier to the environment, thereby protecting its host. Let's look at the immunological barrier more closely.
Epithelial cells express PRRs, including TLRs, which respond to PAMPs and DAMPs in the environment. Once activated, these epithelial cells release an array of cytokines and chemokines.
The chemokines that are released include MCP-1 and 4 which attract DC precursors, such as monocytes, and CCL20 which attracts mature DCs and especially those that have been exposed to house dust mite (HDM) as HDM upregulates the receptor for CCL20 called CCR6 on DCs. These DCs are then subject to the cytokines that the epithelium releases like GM-CSF, IL-1β, but most importantly thymic stromal lymphopoietin (TSLP).
TSLP produced by epithelial cells promotes DC survival, activation and maturation but also reduces the levels of IL-12 that DCs produce. With limited levels of IL-12 around during activation, the naive T cell will change into a so called Th2 cell which promotes allergy amongst other things and that we will learn more about in the next module. TSLP also upregulates a molecule called OX40 ligand on DCs, which also can make already existing Th2 cell expand when it binds to OX40 on the T cell surface. Don't you think the combination of TSLP, epithelial cells and DCs seem to point towards promoting allergic inflammation? If so, how do allergens fit into this picture? Take a look at the graphic. What is going on with the epithelial cell in contact with the DerP1 allergen? DerP1 or Dermatophagoides pteronissinus is a protease found in the faeces of house dust mites, which is enzymatically active and, as you can see here, it can physically damage or disrupt the epithelial barrier. DerP1 and some other allergens can also activate a group of receptors called protease-activated receptors (PAR) on the surface of epithelium leading to release of cytokines including TSLP. So what do you think will happen when all these danger signals and cytokines bursting out reaches the nearby DC?...