Researchers led by the Institute of Science Tokyo have discovered that tristetraprolin (TTP) regulates inflammatory responses in basophils, paving the way for new treatments for allergic diseases.
A new breakthrough in the understanding of allergic inflammation has been unveiled by researchers led by the Institute of Science Tokyo, spotlighting the pivotal role of a protein called tristetraprolin (TTP) in basophils.
Inflammation is a fundamental aspect of the body’s defense system, essential for combating infections and repairing tissue damage. Basophils, though constituting less than 1% of white blood cells, have emerged as significant triggers of allergic responses through the release of pro-inflammatory cytokines like IL-4.
Led by Kensuke Miyake, a professor at the Institute of Science Tokyo, the team investigated TTP, an RNA-binding protein, and its influence on basophils. The study, published in Allergology International, reveals that TTP is crucial for degrading mRNAs that encode inflammatory cytokines and chemokines, thus controlling basophil inflammatory responses.
“In this study, we used wild-type and TTP-knockout mice to explore the role of TTP in basophils,” Miyake said in a news release. “Basophils from each strain were stimulated with antigen combined with IgE, IL-33, or lipopolysaccharide (LPS). We measured gene expression, mRNA stability, and inflammatory protein levels.”
The researchers employed advanced techniques such as RNA sequencing (RNA-seq) and SLAM-seq to analyze gene expression and mRNA stability on a transcriptome-wide scale. Using genetically engineered basophil-specific TTP-knockout mice, they further explored the real-world implications of TTP deficiency in an oxazolone-induced atopic dermatitis model.
The findings were significant. When basophils were stimulated with antigen/IgE, IL-33 or LPS, TTP expression was notably upregulated, helping to degrade mRNAs and prevent excessive cytokine production. In the absence of TTP, mRNAs encoding critical inflammatory molecules like Il4, Il13, Areg, Ccl3, Cxcl2 and Ptgs2 remained stable for longer periods, resulting in elevated cytokine and chemokine production.
Miyake emphasized the study’s importance, adding: “By promoting the degradation of mRNA for inflammatory molecules, TTP prevents their overproduction. In the absence of TTP, mRNA remains stable for a longer period, leading to excessive cytokine production and exacerbated allergic responses.”
This research identifies TTP as a significant regulator of inflammatory responses in basophils and suggests that targeting TTP or its pathways could lead to novel treatments for allergic diseases, such as asthma and atopic dermatitis.