Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway

Abstract

Background Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a critical signaling molecule in thymocyte development. This study aimed to investigate the regulatory effect of Tespa1 on mast cells in the pathogenesis of asthma and its relationship with the interleukin (IL)-4/signal transducers and activators of transcription 6 (STAT6) signaling pathway. Methods Tespa1 mRNA expression analysis and IgE levels were carried out using the induced sputum of 33 adults with stable asthma and 36 healthy controls. Tespa1-knockout mice (Tespa1−/−, KO) and C57BL/6 background (wild-type, WT) mice were sensitized and treated with ovalbumin (OVA) to establish an asthma model. Pathological changes, number and activity of mast cells, and changes in activation of the IL-4/STAT6 pathway in lung tissue were detected. The changes of tryptase expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The changes of enzyme expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The association between the Tespa1 and p-STAT6 was analyzed by co-immunoprecipitation method. Results Compared with the healthy controls, Tespa1 expression was decreased, and IgE levels were elevated in the sputum of asthmatic patients. Animal experiments showed that Tespa1−/− mice exhibited more severe inflammation, higher quantity of goblet cells and mast cells in the bronchium, and greater expression of mast cell tryptase, which is induced by ovalbumin, than WT mice. And IL-4, IL-13, phospho-Janus kinase 1, and p-STAT6 expressions presented a higher increase in the Tespa1−/− mouse model than in the WT mouse model. Further in vitro studies confirmed that IL-4 could more significantly promote tryptase and p-STAT6 activities in Tespa1−/− mast cells than their WT counterparts. Correlation analysis results showed a negative correlation between Tespa1 and p-STAT6. Co-immunoprecipitation results demonstrated an association between Tespa1 and p-STAT6. Conclusions Altogether, our results indicate that Tespa1 can negatively regulate mast cell activity, and this event is related to the mast cell IL-4/STAT6 signaling pathway and could be therapeutically exploited to treat asthma attacks.

Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging

“…TESPA1 is involved in the development and maturation of T-cells and plays a critical role in immune defects in the elderly [ 62 ]. Furthermore, animal models have shown that TESPA1- knockout mice ( Tespa1 −/− , KO) exhibit more severe inflammation [ 63 ]. Given that a critical component of aging is a set of functional and structural changes in the immune system that manifests in reduced B and T cell production [ 62 ], genetic variation in TESPA1 might influence the aging process.…”

A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model

“…BALB/c and C57BL/ 6 mice are commonly used as model animals for allergic rhinitis. [2][3][4] However, when given identical sensitization and challenge protocols, the two types of mice exhibit different levels of airway responsiveness. 5 For example, BALB/c mice developed more severe allergic rhinitis than the C57BL/6 mice when the Schistosoma mansoni egg was used.…”

Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation

“…In addition, Tespa1 is reported to be involved in the regulation of the proliferation and function of B cells probably via the CD40/TRAF6 axis [ 21 ]. Recent researches show that Tespa1 also participates in the activation of mast cells, thereby modulating allergic response and airway hyperreactivity [ 22 , 23 ]. These findings indicate that Tespa1 is a crucial regulator of the immune system.…”