@article{a011c2f827d840db917ffacaeb65fe65,
title = "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.",
keywords = "ILC, LTi cell, Peyer's patch, SAVI, STING, STING-associated vasculopathy with onset in infancy, innate lymphoid cell, lymph node, lymphoid tissue organogenesis, lymphopoiesis",
author = "Bennion, {Brock G.} and Croft, {Carys A.} and Ai, {Teresa L.} and Wei Qian and Menos, {Amber M.} and Miner, {Cathrine A.} and Fr{\'e}mond, {Marie Louis} and Doisne, {Jean Marc} and Andhey, {Prabhakar S.} and Platt, {Derek J.} and Bando, {Jennifer K.} and Wang, {Erin R.} and Hella Luksch and Molina, {Thierry J.} and Roberson, {Elisha D.O.} and Artyomov, {Maxim N.} and Angela R{\"o}sen-Wolff and Marco Colonna and Fr{\'e}d{\'e}ric Rieux-Laucat and {Di Santo}, {James P.} and B{\'e}n{\'e}dicte Neven and Miner, {Jonathan J.}",
note = "Funding Information: We thank the Hope Center Transgenic Vectors Core for assistance with generation of transgenic mice and the Washington University Morphology and Imaging Core for assistance with tissue processing and staining. D.J.P. is supported by the Washington University Chancellors Graduate Fellowship Program and the Initiative to Maximize Student Development . The Miner laboratory is supported by grants from the NIH ( K08 AR070918 and R01 AI143982 ). RNA sequencing data analysis was supported by the WUSTL Rheumatic Diseases Research Resource-based Core (E.D.O.R., P30-AR073752 ). Single-cell RNA-seq data were generated at the Washington University GTAC MGI sequencing core, which is partially supported by NCI grant P30 CA91842 (Siteman Cancer Center) and ICTS/CTSA grant UL1 TR002345 . C.A.C. is part of the Pasteur-Paris University (PPU) International PhD Program that received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 665807 and from the Labex Revive, Institut Pasteur . The study was also supported by the Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), by a government grant managed by the Agence National de la Recherche as part of the “Investment for the Future” program ( ANR-10-IAHU-01 ), and by an AAPG grant from the Agence National de la Recherche ( ANR-14-CE14-0026-01 “Lumugene” to F.R.-L.). The R{\"o}sen-Wolff laboratory is supported by the German Research Foundation ( TRR237 , B18 ). Funding Information: We thank the Hope Center Transgenic Vectors Core for assistance with generation of transgenic mice and the Washington University Morphology and Imaging Core for assistance with tissue processing and staining. D.J.P. is supported by the Washington University Chancellors Graduate Fellowship Program and the Initiative to Maximize Student Development. The Miner laboratory is supported by grants from the NIH (K08 AR070918 and R01 AI143982). RNA sequencing data analysis was supported by the WUSTL Rheumatic Diseases Research Resource-based Core (E.D.O.R. P30-AR073752). Single-cell RNA-seq data were generated at the Washington University GTAC MGI sequencing core, which is partially supported by NCI grant P30 CA91842 (Siteman Cancer Center) and ICTS/CTSA grant UL1 TR002345. C.A.C. is part of the Pasteur-Paris University (PPU) International PhD Program that received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 665807 and from the Labex Revive, Institut Pasteur. The study was also supported by the Institut National de la Sant? et de la Recherche M?dicale (INSERM), by a government grant managed by the Agence National de la Recherche as part of the ?Investment for the Future? program (ANR-10-IAHU-01), and by an AAPG grant from the Agence National de la Recherche (ANR-14-CE14-0026-01 ?Lumugene? to F.R.-L.). The R?sen-Wolff laboratory is supported by the German Research Foundation (TRR237,B18). B.G.B. C.A.C. T.L.A. W.Q. A.M.M. C.A.M. J.-M.D. E.R.W. J.K.B. H.L. M.-L.F. and D.J.P. performed experiments. B.G.B. C.A.C, T.L.A. W.Q. A.M.M. C.A.M. J.-M.D. J.K.B. P.S.A. D.J.P. T.J.M. A.R.-W. E.D.O.R. M.N.A. F.R.-L. J.P.D.S. B.N. and J.J.M. analyzed data. A.R.-W. M.C. F.R.-L. J.P.D. B.N. and J.J.M. guided experiments. B.G.B. and T.L.A. wrote portions of the initial manuscript and edited subsequent versions of the manuscript. J.J.M. edited and wrote the final version of the manuscript. All authors reviewed and edited the final version of the manuscript. J.J.M. conceived the project and directed all experiments. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = jun,
day = "16",
doi = "10.1016/j.celrep.2020.107771",
language = "English",
volume = "31",
journal = "Cell Reports",
issn = "2211-1247",
number = "11",
}