Interleukin-31 Receptor and neurogenic inflammation
Final Report Abstract
The mechanisms how nerve cells communicate with immune cells during inflammation, inflammatory pain or pruritus are only poorly understood. One of the skin diseases in which the neurogenic aspect plays an essential role for the mediation of inflammation (erythematic, vasodilatation, recruitment of inflammatory cells to the site of inflammation) and itching is atopic dermatitis (AD). The underlying molecular and cellular mechanisms how the nervous system communicates with the immune system in atopic dermatitis, however, are poorly investigated. Recently, interleukin (IL)-31 has been demonstrated to be up-regulated in atopic dermatitis by activating the oncostatin M receptor (OSMR) and IL-31 receptor A (IL-31RA) complex. With others, we found that IL-31RA is expressed by murine and human sensory neurons and may thus be involved in neurogenic inflammation, pain and/ or pruritus. However, the biological function of this novel neuroimmune pathway, especially with respect to communication with other neuronal receptors (Protease-activated receptors (PARs), TRPV channels neuropeptide receptors) is completely unknown. Therefore, during the funding period I investigated the relevance of IL-31 and its receptor complex in itch sensation as well as in pain transmission. Moreover, I studied the possible cross-talk of IL-31RA, subunit of the IL-31 Receptor complex, with neuronal receptors and marker molecules in the peripheral and central nervous system. Additionally, I defined the signalling pathways of IL-31 mediated effects in neuronal cells for itch transmission on peripheral levels and delineated a functional role of a cytokine and its receptor on itch on central levels of the nervous system.
