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

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03153086
Contributor : Carys Anne Croft <>
Submitted on : Friday, February 26, 2021 - 9:31:38 AM
Last modification on : Thursday, June 10, 2021 - 6:02:02 PM
Long-term archiving on: : Thursday, May 27, 2021 - 6:13:42 PM

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Brock Bennion, Carys Croft, Teresa Ai, Wei Qian, Amber Menos, et al.. STING Gain-of-Function Disrupts Lymph Node Organogenesis and Innate Lymphoid Cell Development in Mice. Cell Reports, Elsevier Inc, 2020, 31 (11), pp.107771. ⟨10.1016/j.celrep.2020.107771⟩. ⟨pasteur-03153086⟩

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