Human group3 innate lymphoid cells express DR3 and respond to TL1A with enhanced IL-22 production and IL-2-dependent proliferation.
Eur J Immunol
; 45(8): 2335-42, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26046454
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 ILC3s with exogenous TL1A alone had no impact on cytokine production or proliferation. Addition of TL1A to IL-1ß + IL-23 significantly enhanced the amount IL-22 produced by ILC3s as well as the percentage IL-22- and IL-8-producing cells. Addition of TL1A to IL-1ß + IL-23 also augmented ILC3 proliferation. Mechanistically, this occurred through the upregulation of CD25 and responsiveness to IL-2 stimulation. The combination of TL1A, IL-1ß+ IL-23, and IL-2 expanded ILC3s while IL-1ß+ IL-23 did not increase proliferation above controls. After 2 weeks of expansion, ILC3s maintained their phenotype, transcription factor expression, and function (IL-22 production). These findings identify DR3 as a costimulatory molecule on ILC3s that could be exploited for ex vivo expansion and clinical use.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Regulação para Cima
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Interleucinas
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Interleucina-2
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Proliferação de Células
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Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral
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Membro 25 de Receptores de Fatores de Necrose Tumoral
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Imunidade Inata
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article