Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells
Autor: | Fengrui Zhang, Xujun Ye, Zhou Zhu, Lihui Wang, Haiying Tang, Li Zhou, Tao Zheng, William G. Kerr, Zi Chen, Li Zhang, Yadong Wei |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cell type Science Immunology Innate lymphoid cells Inflammation Biology Article Allergic inflammation Mice 03 medical and health sciences 0302 clinical medicine Immune system Papain medicine Animals Lymphocytes PI3K/AKT/mTOR pathway Mice Knockout Multidisciplinary Innate immune system Innate lymphoid cell Pneumonia Hematopoietic Stem Cells Fibrosis Immunity Innate Asthma Mice Inbred C57BL Innate immune cells Haematopoiesis 030104 developmental biology Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Cancer research Medicine medicine.symptom 030215 immunology |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Src homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation. |
Databáze: | OpenAIRE |
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