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Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues.
Nat Commun. 2020 Jul 09; 11(1):3421.NC

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.

Authors+Show Affiliations

Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Med. Klinik m.S. Gastroenterologie, Infektiologie und Rheumatologie and Deutsches Rheuma-Forschungszentrum, Charité - Universitätsmedizin Berlin, Berlin, Germany.Med. Klinik m.S. Gastroenterologie, Infektiologie und Rheumatologie and Deutsches Rheuma-Forschungszentrum, Charité - Universitätsmedizin Berlin, Berlin, Germany.The Kennedy Institute of Rheumatology, The University of Oxford, Oxford, UK.Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.Department of Medicine, Centre for Inflammatory Disease, Imperial College London, London, UK.Division of Medical and Molecular Genetics and Immunology, Infection and Inflammatory Disease, King's College London, London, UK.Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. d.withers@bham.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32647184

Citation

Gajdasik, Dominika W., et al. "Th1 Responses in Vivo Require Cell-specific Provision of OX40L Dictated By Environmental Cues." Nature Communications, vol. 11, no. 1, 2020, p. 3421.
Gajdasik DW, Gaspal F, Halford EE, et al. Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues. Nat Commun. 2020;11(1):3421.
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), 3421. https://doi.org/10.1038/s41467-020-17293-3
Gajdasik DW, et al. Th1 Responses in Vivo Require Cell-specific Provision of OX40L Dictated By Environmental Cues. Nat Commun. 2020 Jul 9;11(1):3421. PubMed PMID: 32647184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues. AU - Gajdasik,Dominika W, AU - Gaspal,Fabrina, AU - Halford,Emily E, AU - Fiancette,Remi, 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, Y1 - 2020/07/09/ PY - 2019/01/07/received PY - 2020/06/23/accepted PY - 2020/7/11/entrez PY - 2020/7/11/pubmed PY - 2020/7/11/medline SP - 3421 EP - 3421 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/32647184/Th1_responses_in_vivo_require_cell-specific_provision_of_OX40L_dictated_by_environmental_cues L2 - http://dx.doi.org/10.1038/s41467-020-17293-3 DB - PRIME DP - Unbound Medicine ER -
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