Expression and Function of The TNF-Superfamily Receptor DR3 in Human Group 3 Innate Lymphoid Cells
| Autor: | Ahn, Yong-Oon, Weeres, Matthew A., Neulen, Marie-Luise, Choi, Jahyang, Kang, Seong-Ho, Heo, Dae Seog, Bergerson, Rachel, Blazar, Bruce R., Miller, Jeffrey S., Verneris, Michael R. |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Tumor Necrosis Factor Ligand Superfamily Member 15
Interleukins Interleukin-1beta Interleukin-8 Interleukin-2 Receptor alpha Subunit Article Immunity Innate Up-Regulation Interleukin-23 Subunit p19 Humans Interleukin-2 Lymphocytes Receptors Tumor Necrosis Factor Member 25 Cells Cultured Cell Proliferation |
| Popis: | Death receptor 3 (DR3, TNFRSF25) is expressed by activated lymphocytes and signaling by its ligand, TL1A, enhances cytokine expression and proliferation. Recent studies show that DR3 is also present on murine type 2 innate lymphoid cells (ILC2s). Here, we show that DR3 is expressed by IL-22 producing human group 3 innate lymphoid cells (ILC3s). Stimulation of ILC3 cells with exogenous TL1A alone had no impact on cytokine production or proliferation. Addition of TL1A to IL-1β + IL-23 significantly enhanced the amount IL-22 produced by ILC3 cells as well as the percentage IL-22 and IL-8 producing cells. Addition of TL1A to IL-1β + IL-23 also augmented ILC3 proliferation in short term (5 day assays). Mechanistically, this occurred through the up-regulation of CD25 and responsiveness to IL-2 stimulation. The combination of TL1A, IL-1β+ IL-23 and IL-2 expanded ILC3 cells (39.3 fold) while IL-1β+ IL-23 did not increase proliferation above controls. After two weeks of expansion, ILC3 cells maintained their phenotype, transcription factor expression and function (IL-22 production). These findings identify DR3 as a costimulatory molecule on ILC3 cells that can be exploited for ex vivo expansion and clinical use. |
| Databáze: | OpenAIRE |
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