IL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration
| Autor: | Marina Pretolani, Yashaswi Shrestha, Jingya Wang, Fatima Hamidi, Roland Kolbeck, Jincheng Wu, Michel Aubier, Valérie Besnard, Alison A. Humbles, Alan M. Copenhaver, Rania Dagher, Aaron A Berlin, Xiaotao Qu, Rajiv Raja, Gregory Gautier, Marielle Maret |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Alveolar macrophages
0301 basic medicine Science General Physics and Astronomy Biology Lymphocyte Activation Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Myeloid Cell Differentiation medicine Regeneration Animals Lymphocytes lcsh:Science Bronchioles Lung Adult stem cells Mice Knockout Multidisciplinary Interleukins Macrophages Monocyte Regeneration (biology) Innate lymphoid cell Cell Differentiation Epithelial Cells General Chemistry Cell cycle Interleukin-33 Interleukin-1 Receptor-Like 1 Protein Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Monocyte differentiation Cytokines Female lcsh:Q Signal transduction Signal Transduction Adult stem cell |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-19 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Evidence points to an indispensable function of macrophages in tissue regeneration, yet the underlying molecular mechanisms remain elusive. Here we demonstrate a protective function for the IL-33-ST2 axis in bronchial epithelial repair, and implicate ST2 in myeloid cell differentiation. ST2 deficiency in mice leads to reduced lung myeloid cell infiltration, abnormal alternatively activated macrophage (AAM) function, and impaired epithelial repair post naphthalene-induced injury. Reconstitution of wild type (WT) AAMs to ST2-deficient mice completely restores bronchial re-epithelialization. Central to this mechanism is the direct effect of IL-33-ST2 signaling on monocyte/macrophage differentiation, self-renewal and repairing ability, as evidenced by the downregulation of key pathways regulating myeloid cell cycle, maturation and regenerative function of the epithelial niche in ST2−/− mice. Thus, the IL-33-ST2 axis controls epithelial niche regeneration by activating a large multi-cellular circuit, including monocyte differentiation into competent repairing AAMs, as well as group-2 innate lymphoid cell (ILC2)-mediated AAM activation. Signaling of IL-33 via its receptor, ST2, has been implicated in macrophage function in tissue repair. Here the authors show, using genetic mouse models and single-cell transcriptomic data, that the IL-33/ST2 axis regulates both ILC2-derived IL-13 and macrophage differentiation/reparative function required for club cell regeneration. |
| Databáze: | OpenAIRE |
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