STING Gain-of-Function Disrupts Lymph Node Organogenesis and Innate Lymphoid Cell Development in Mice

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Brock G. Bennion - , Washington University St. Louis (Author)
  • Carys A. Croft - , Institut Pasteur Paris, Sorbonne Université (Author)
  • Teresa L. Ai - , Washington University St. Louis (Author)
  • Wei Qian - , Washington University St. Louis (Author)
  • Amber M. Menos - , Washington University St. Louis (Author)
  • Cathrine A. Miner - , Washington University St. Louis (Author)
  • Marie-Louis Frémond - , Necker–Enfants Malades Hospital (Author)
  • Jean-Marc Doisne - , Institut Pasteur Paris, Sorbonne Université (Author)
  • Prabhakar S. Andhey - , Washington University St. Louis (Author)
  • Derek J. Platt - , Washington University St. Louis (Author)
  • Jennifer K. Bando - , Washington University St. Louis (Author)
  • Erin R. Wang - , Washington University St. Louis (Author)
  • Hella Luksch - , Department of Paediatrics (Author)
  • Thierry J. Molina - , Necker–Enfants Malades Hospital (Author)
  • Elisha D.O. Roberson - , Washington University St. Louis (Author)
  • Maxim N. Artyomov - , Washington University St. Louis (Author)
  • Angela Rösen-Wolff - , Department of Paediatrics (Author)
  • Marco Colonna - , Washington University St. Louis (Author)
  • Frédéric Rieux-Laucat - , Imagine Institute (Author)
  • James P. Di Santo - , Institut Pasteur Paris, Sorbonne Université (Author)
  • Bénédicte Neven - , Necker–Enfants Malades Hospital, Imagine Institute (Author)
  • Jonathan J. Miner - , Washington University St. Louis (Author)

Abstract

STING gain-of-function causes autoimmunity and immunodeficiency in mice and STING-associated vasculopathy with onset in infancy (SAVI) in humans. Here, we report that STING gain-of-function in mice prevents development of lymph nodes and Peyer’s patches. We show that the absence of secondary lymphoid organs is associated with diminished numbers of innate lymphoid cells (ILCs), including lymphoid tissue inducer (LTi) cells. Although wild-type (WT) α4β7+ progenitors differentiate efficiently into LTi cells, STING gain-of-function progenitors do not. Furthermore, STING gain-of-function impairs development of all types of ILCs. Patients with STING gain-of-function mutations have fewer ILCs, although they still have lymph nodes. In mice, expression of the STING mutant in RORγT-positive lineages prevents development of lymph nodes and reduces numbers of LTi cells. RORγT lineage-specific expression of STING gain-of-function also causes lung disease. Since RORγT is expressed exclusively in LTi cells during fetal development, our findings suggest that STING gain-of-function prevents lymph node organogenesis by reducing LTi cell numbers in mice.

Details

Original languageEnglish
Article number107771
JournalCell reports
Volume31
Issue number11
Publication statusPublished - 16 Jun 2020
Peer-reviewedYes

External IDs

Scopus 85086399061

Keywords

Keywords

  • STING, ILC, lymphoid tissue organogenesis, lymphopoiesis, SAVI, LTi cell, lymph node, Peyer's patch, STING-associated vasculopathy with onset in infancy, innate lymphoid cell, STING, ILC, lymphoid tissue organogenesis, Lymphopoiesis, SAVI, LTi cell, lymph node, Peyer's patch, STING-associated vasculopathy with onset in infancy, innate lymphoid cell