Interleukin-4 Signaling Pathway and Effects in Allergic Diseases

Title:Interleukin-4 Signaling Pathway and Effects in Allergic Diseases

Volume: 13 Issue: 1

Author(s): N. Philips*, P. Samuel, M. Samuel, G. Perez, R. Khundoker and G. Alahmade

Affiliation:

• School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ 07666,United States

Keywords: Dermatitis, asthma, IL-4, STAT6, apoptosis, fibrosis, lymphocytes.

Abstract: Background: Allergic diseases, such as atopic dermatitis and allergic asthma, are associated with increased inflammation and interleukin-4 (IL-4) signaling. An inhibitor of the IL-4 receptor, dupimulab, was approved recently for dermatitis. This goal of this review is to elucidate the mechanism and effects of IL-4 signaling.

Methods: We reviewed information available in immunology and molecular biology textbooks, and research and review articles to accomplish our goal.

Results: The increased inflammation, in allergic diseases, is due to inflammatory cytokines released from innate leukocytes and local tissue. The increased IL-4 signaling activates the helper Th2 cells to release IL-4, and the allergic effects. The IL-4 binds to its receptors to activate JAK1/JAK3 mediated nuclear translocation of the phosphorylated STAT6 dimer, which stimulates the expression of IgE antibodies in B-cells. The released IgE stimulates the release of histamines from mast cells, alters the expression of genes associated with fibrosis, and induces apoptosis of epidermal or epithelial cells. The resultant IL-4 effects in allergic diseases include pruritus or wheezing, fibrosis and/or altered expression of extracellular matrix proteins, and loss of epidermal or epithelial barrier function.

Conclusion: The specific inhibition of the Il-4 signaling, through dupimulab that binds the IL-4 α receptor subunit, would be effective in the specific inhibition of the allergic response in patients with allergic dermatitis or asthma.

Cite this article as:

Philips N.*, Samuel P. , Samuel M., Perez G., Khundoker R. and Alahmade G., Interleukin-4 Signaling Pathway and Effects in Allergic Diseases, Current Signal Transduction Therapy 2018; 13 (1) . https://dx.doi.org/10.2174/1574362413666180319143151