Role of inflammasome in severe, steroid-resistant asthma

Bariaa A Khalil; Narjes Saheb Sharif-Askari; Rabih Halwani

doi:10.1016/j.crimmu.2023.100061

Role of inflammasome in severe, steroid-resistant asthma

Curr Res Immunol. 2023 Jun 3:4:100061. doi: 10.1016/j.crimmu.2023.100061. eCollection 2023.

Authors

Bariaa A Khalil¹, Narjes Saheb Sharif-Askari², Rabih Halwani^{1

3

4}

Affiliations

¹ Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
² College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
³ Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁴ Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Saudi Arabia.

Abstract

Purpose of review: Asthma is a common heterogeneous group of chronic inflammatory diseases with different pathological phenotypes classified based on the various clinical, physiological and immunobiological profiles of patients. Despite similar clinical symptoms, asthmatic patients may respond differently to treatment. Hence, asthma research is becoming more focused on deciphering the molecular and cellular pathways driving the different asthma endotypes. This review focuses on the role of inflammasome activation as one important mechanism reported in the pathogenesis of severe steroid resistant asthma (SSRA), a Th2-low asthma endotype. Although SSRA represents around 5-10% of asthmatic patients, it is responsible for the majority of asthma morbidity and more than 50% of asthma associated healthcare costs with clear unmet need. Therefore, deciphering the role of the inflammasome in SSRA pathogenesis, particularly in relation to neutrophil chemotaxis to the lungs, provides a novel target for therapy.

Recent findings: The literature highlighted several activators of inflammasomes that are elevated during SSRA and result in the release of proinflammatory mediators, mainly IL-1β and IL-18, through different signaling pathways. Consequently, the expression of NLRP3 and IL-1β is shown to be positively correlated with neutrophil recruitment and negatively correlated with airflow obstruction. Furthermore, exaggerated NLRP3 inflammasome/IL-1β activation is reported to be associated with glucocorticoid resistance.

Summary: In this review, we summarized the reported literature on the activators of the inflammasome during SSRA, the role of IL-1β and IL-18 in SSRA pathogenesis, and the pathways by which inflammasome activation contributes to steroid resistance. Finally, our review shed light on the different levels to target inflammasome involvement in an attempt to ameliorate the serious outcomes of SSRA.

Keywords: IL-18; IL-1β; Inflammasome; Neutrophilic asthma; Pyroptosis; Severe steroid resistant asthma (SSRA).

Publication types

Review