STING Gain-of-Function Disrupts Lymph Node Organogenesis and Innate Lymphoid Cell Development in Mice
Brock G. Bennion, Carys A. Croft, Teresa L. Ai, Wei Qian, Amber M. Menos, Cathrine A. Miner, Marie-Louis Frémond, Jean‐Marc Doisne, Prabhakar S. Andhey, Derek J. Platt, Jennifer K. Bando, Erin R. Wang, Hella Luksch, Thierry Jo Molina, Elisha Roberson, Maxim N. Artyomov, Angela Rösen‐Wolff, Marco Colonna, Frédéric Rieux‐Laucat, James P. Di Santo, Bénédicte Neven, Jonathan J. Miner
Abstract
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.