Peripheral PDGFRα+gp38+ mesenchymal cells support the differentiation of fetal liver–derived ILC2
| Autor: | Ken-ichi Hirano, Masaki Yazawa, Shigeo Koyasu, Katsuto Hozumi, Kazuyo Moro, Takashi Nagasawa, Tommy Terooatea, Satoshi Koga, Aki Minoda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stromal cell Receptor Platelet-Derived Growth Factor alpha Liver cytology T-Lymphocytes Immunology Notch signaling pathway GATA3 Transcription Factor Thymus Gland Biology Article 03 medical and health sciences 0302 clinical medicine Fetus Growth factor receptor Immunology and Allergy Animals Cell Lineage Mesentery Lymphocytes Progenitor cell Transcription factor Research Articles B-Lymphocytes Membrane Glycoproteins Receptors Notch Interleukin-7 Mesenchymal stem cell Innate lymphoid cell Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Differentiation Mesenchymal Stem Cells Lymphoid Progenitor Cells Immunity Innate Cell biology Mice Inbred C57BL 030104 developmental biology Liver Stromal Cells 030215 immunology Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | We demonstrate that the quantity of IL-7 and Notch signaling differentially regulate lymphocyte fate. We also identify ILC progenitor and immature ILC2 in the fetal mesentery, which are terminally differentiated and matured by PDGFRα+gp38+ mesenchymal cells. Group 2 innate lymphoid cells (ILC2s) are derived from common lymphoid progenitors (CLPs) via several specific precursors, and the transcription factors essential for ILC2 differentiation have been extensively studied. However, the external factors regulating commitment to the ILC lineage as well as the sites and stromal cells that constitute the optimal microenvironment for ILC2-specific differentiation are not fully defined. In this study, we demonstrate that three key external factors, the concentration of interleukin 7 (IL-7) and strength and duration of Notch signaling, coordinately determine the fate of CLP toward the T, B, or ILC lineage. Additionally, we identified three stages of ILC2 in the fetal mesentery that require STAT5 signals for maturation: ILC progenitors, CCR9+ ILC2 progenitors, and KLRG1− immature ILC2. We further demonstrate that ILC2 development is supported by mesenteric platelet-derived growth factor receptor α (PDGFRα)+ glycoprotein 38 (gp38)+ mesenchymal cells. Collectively, our results suggest that early differentiation of ILC2 occurs in the fetal liver via IL-7 and Notch signaling, whereas final differentiation occurs in the periphery with the aid of PDGFRα+gp38+ cells. Graphical Abstract |
| Databáze: | OpenAIRE |
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