Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues

Dominika W Gajdasik; Fabrina Gaspal; Emily E Halford; Remi Fiancette; Emma E Dutton; Claire Willis; Timo Rückert; Chiara Romagnani; Audrey Gerard; Sarah L Bevington; Andrew S MacDonald; Marina Botto; Timothy Vyse; David R Withers

doi:10.1038/s41467-020-17293-3

Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues

Dominika W Gajdasik, Fabrina Gaspal, Emily E Halford, Remi Fiancette, Emma E Dutton, Claire Willis, Timo Rückert, Chiara Romagnani, Audrey Gerard, Sarah L Bevington, Andrew S MacDonald, Marina Botto, Timothy Vyse, David R Withers

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Abstract

The OX40-OX40L pathway provides crucial co-stimulatory signals for CD4 T cell responses, however the precise cellular interactions critical for OX40L provision in vivo and when these occur, remains unclear. Here, we demonstrate that provision of OX40L by dendritic cells (DCs), but not T cells, B cells nor group 3 innate lymphoid cells (ILC3s), is critical specifically for the effector Th1 response to an acute systemic infection with Listeria monocytogenes (Lm). OX40L expression by DCs is regulated by cross-talk with NK cells, with IFNγ signalling to the DC to enhance OX40L in a mechanism conserved in both mouse and human DCs. Strikingly, DC expression of OX40L is redundant in a chronic intestinal Th1 response and expression by ILC3s is necessary. Collectively these data reveal tissue specific compartmentalisation of the cellular provision of OX40L and define a mechanism controlling DC expression of OX40L in vivo.

Original language	English
Article number	3421
Number of pages	15
Journal	Nature Communications
Volume	11
Issue number	1
Early online date	9 Jul 2020
DOIs	https://doi.org/10.1038/s41467-020-17293-3
Publication status	Published - Dec 2020

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Gajdasik_et_al_Th1_responses_in_vivo_require_cell-specific_Nature_Communications_2020Final published version, 2.64 MBLicence: Creative Commons: Attribution (CC BY)

ILC3 control of adaptive immune responses
Withers, D.
THE WELLCOME TRUST
1/04/16 → 30/09/21
Project: Research

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Gajdasik, D. W., Gaspal, F., Halford, E. E., Fiancette, R., Dutton, E. E., Willis, C., Rückert, T., Romagnani, C., Gerard, A., Bevington, S. L., MacDonald, A. S., Botto, M., Vyse, T., & Withers, D. R. (2020). Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues. Nature Communications, 11(1), Article 3421. Advance online publication. https://doi.org/10.1038/s41467-020-17293-3

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abstract = "The OX40-OX40L pathway provides crucial co-stimulatory signals for CD4 T cell responses, however the precise cellular interactions critical for OX40L provision in vivo and when these occur, remains unclear. Here, we demonstrate that provision of OX40L by dendritic cells (DCs), but not T cells, B cells nor group 3 innate lymphoid cells (ILC3s), is critical specifically for the effector Th1 response to an acute systemic infection with Listeria monocytogenes (Lm). OX40L expression by DCs is regulated by cross-talk with NK cells, with IFNγ signalling to the DC to enhance OX40L in a mechanism conserved in both mouse and human DCs. Strikingly, DC expression of OX40L is redundant in a chronic intestinal Th1 response and expression by ILC3s is necessary. Collectively these data reveal tissue specific compartmentalisation of the cellular provision of OX40L and define a mechanism controlling DC expression of OX40L in vivo.",

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AU - Dutton, Emma E

AU - Willis, Claire

AU - Rückert, Timo

AU - Romagnani, Chiara

AU - Gerard, Audrey

AU - Bevington, Sarah L

AU - MacDonald, Andrew S

AU - Botto, Marina

AU - Vyse, Timothy

AU - Withers, David R

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Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues

Abstract

ASJC Scopus subject areas

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ILC3 control of adaptive immune responses

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