STING Gain-of-Function Disrupts Lymph Node Organogenesis and Innate Lymphoid Cell Development in Mice
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Article number | 107771 |
Journal | Cell reports |
Volume | 31 |
Issue number | 11 |
Publication status | Published - 16 Jun 2020 |
Peer-reviewed | Yes |
External IDs
Scopus | 85086399061 |
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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