Related Experiment Video
Updated: Jul 9, 2025

Isolation and Quantitative Evaluation of Brush Cells from Mouse Tracheas
Published on: June 12, 2019
The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2
Jin Kumagai1,2, Masahiro Kiuchi1, Kota Kokubo1
1Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Abstract:
Uncontrolled type 2 immunity by type 2 helper T (Th2) cells causes intractable allergic diseases; however, whether the interaction of CD4+ T cells shapes the pathophysiology of allergic diseases remains unclear. We identified a subset of Th2 cells that produced the serine proteases granzyme A and B early in differentiation. Granzymes cleave protease-activated receptor (Par)-1 and induce phosphorylation of p38 mitogen-activated protein kinase (MAPK), resulting in the enhanced production of IL-5 and IL-13 in both mouse and human Th2 cells. Ubiquitin-specific protease 7 (USP7) regulates IL-4-induced phosphorylation of STAT3, resulting in granzyme production during Th2 cell differentiation. Genetic deletion of Usp7 or Gzma and pharmacological blockade of granzyme B ameliorated allergic airway inflammation. Furthermore, PAR-1+ and granzyme+ Th2 cells were colocalized in nasal polyps from patients with eosinophilic chronic rhinosinusitis. Thus, the USP7-STAT3-granzymes-Par-1 pathway is a potential therapeutic target for intractable allergic diseases.
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The JAK-STAT Signaling Pathway
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
TGF - β Signaling Pathway
Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:

