Memory-type ST2+CD4+T cells participate in the steroid-resistant pathology of eosinophilic pneumonia

The lung develops an unique epithelial barrier system to protect host from continuous invasion of various harmful particles. Interleukin (IL-)33 released from epithelial cells in the lung drives the type 2 immune response by activating ST2-expressed immune cells in various allergic diseases. However, the involvement of memory-type ST2(+)CD4(+)T cells in such lung inflammation remains unclear. Here we demonstrated that intratracheal administration of IL-33 resulted in the substantial increase of numbers of tissue-resident memory-type ST2(+)CD4(+)T cells in the lung. Following enhanced production of IL-5 and IL-13, eosinophilic lung inflammation sequentially developed. IL-33-mediated eosinophilic lung inflammation was not fully developed in T cell-deficient Foxn1(nu) mice and NSG mice. Dexamethasone treatment showed limited effects on both the cell number and function of memory-type ST2(+)CD4(+)T cells. Thus our study provides novel insight into the pathogenesis of eosinophilic lung disease, showing that memory-type ST2(+)CD4(+)T cells are involved in IL-33-induced eosinophilic inflammation and elicited steroid-resistance.