The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+ CD4+ T cells

Abstract

The lungs are the primary organs of the respiratory system in many animals and have unique epithelial barrier systems to protect the host from continuous invasion of various harmful particles, such as viruses and bacteria. IL-33, a member of the IL-1 family of cytokines, is released from epithelial cells in the mucosal organs and drives the type 2 immune response by activating a number of immune cells in cases of helminth infection. However, IL-33 derived from epithelial cells also causes various allergic diseases via the activation of ST2-positive immune cells, including memory-type (CD62L^low CD44^hi ) ST2⁺ CD4⁺ T cells in the lung. Recent studies have revealed that the type 2 inflammation induced by IL-33 is steroid resistant. Steroid resistance causes severe chronic inflammatory diseases, such as intractable asthma. In this review, we will discuss the impact of ST2⁺ CD4⁺ T cells on shaping the pathology of IL-33-induced eosinophilic inflammation. We will also highlight the mechanism underlying steroid resistance in eosinophilic pneumonia. A better understanding of the cellular and molecular mechanisms underlying steroid resistance is crucial for the development of new therapeutic strategies for intractable allergic diseases.

Keywords: eosinophilic pneumonia; epithelial cytokine; iBALT; pathogenic Th2.