1. Activation of ILC2s through constitutive IFNγ signaling reduction leads to spontaneous pulmonary fibrosis.
- Author
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Otaki N, Motomura Y, Terooatea T, Thomas Kelly S, Mochizuki M, Takeno N, Koyasu S, Tamamitsu M, Sugihara F, Kikuta J, Kitamura H, Shiraishi Y, Miyanohara J, Nagano Y, Saita Y, Ogura T, Asano K, Minoda A, and Moro K
- Subjects
- Animals, Mice, Immunity, Innate, Interleukin-33 genetics, Lymphocytes, Fibrosis, Collagen, Lung pathology, Mice, Inbred C57BL, Interleukin-1 Receptor-Like 1 Protein, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis genetics, Pulmonary Fibrosis pathology
- Abstract
Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the bleomycin-induced PF mouse model has improved our understanding of exogenous factor-induced fibrosis, the mechanism governing endogenous factor-induced fibrosis remains unknown. Here, we find that Ifngr1
-/- Rag2-/- mice, which lack the critical suppression factor for group 2 innate lymphoid cells (ILC2), develop PF spontaneously. The onset phase of fibrosis includes ILC2 subpopulations with a high Il1rl1 (IL-33 receptor) expression, and fibrosis does not develop in ILC-deficient or IL-33-deficient mice. Although ILC2s are normally localized near bronchioles and blood vessels, ILC2s are increased in fibrotic areas along with IL-33 positive fibroblasts during fibrosis. Co-culture analysis shows that activated-ILC2s directly induce collagen production from fibroblasts. Furthermore, increased IL1RL1 and decreased IFNGR1 expressions are confirmed in ILC2s from individuals with idiopathic PF, highlighting the applicability of Ifngr1-/- Rag2-/- mice as a mouse model for fibrosis research., (© 2023. The Author(s).)- Published
- 2023
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