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

N Mato, K Hirahara, T Ichikawa, J Kumagai… - Scientific reports, 2017 - nature.com
N Mato, K Hirahara, T Ichikawa, J Kumagai, M Nakayama, H Yamasawa, M Bando…
Scientific reports, 2017nature.com
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 …
Abstract
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 Foxn1nu 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.
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