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

Research output: Contribution to journalArticle

Authors

  • Dominika W Gajdasik
  • Emily E Halford
  • Emma E Dutton
  • Claire Willis
  • Timo Rückert
  • Chiara Romagnani
  • Audrey Gerard
  • Andrew S MacDonald
  • Marina Botto
  • Timothy Vyse

External organisations

  • Walter-Brendel-Center of Experimental Medicine, Ludwig-Maximilians Universität Munich, Munich, Germany Munich Heart Alliance, Munich, Germany German Center for Cardiovascular Research, Munich, Germany.
  • The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  • Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
  • Department of Life Sciences, Imperial College London, London, UK
  • King's Health Partners Cancer Biobank, King's College London, London, UK.

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.

Details

Original languageEnglish
Article number3421
Number of pages15
JournalNature Communications
Volume11
Issue number1
Publication statusPublished - 9 Jul 2020