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, Computer Science, University of Virginia, Charlottesville, VA, School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ 07666, School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ 07666, School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ 07666, School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ 07666
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.
