@article{1512031ce2bd4cd792a604bb703e32e5,
title = "Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function",
abstract = "Monogenic errors of the Janus kinase (JAK) family, essential signal transduction hubs of the immune system, have dire consequences in immune function. Gruber et al. describe a JAK1 gain-of-function mutation with mosaicism and monoallelic expression that underlies a multi-system autoinflammatory disease, which is rescued by JAK inhibitor therapy.",
keywords = "JAK inhibitors, JAK-STAT signaling, JAK1, cytokine signaling, inborn errors of immunity, monoallelic expression, mosaicis, precision medicine",
author = "Gruber, {Conor N.} and Calis, {Jorg J.A.} and Sofija Buta and Gilad Evrony and Martin, {Jerome C.} and Uhl, {Skyler A.} and Rachel Caron and Lauren Jarchin and David Dunkin and Robert Phelps and Webb, {Bryn D.} and Saland, {Jeffrey M.} and Miriam Merad and Orange, {Jordan S.} and Mace, {Emily M.} and Rosenberg, {Brad R.} and Gelb, {Bruce D.} and Dusan Bogunovic",
note = "Funding Information: We thank Adeeb Rahman, Brian Lee, Kevin Tuballes, and Laura Walker from the Human Immune Monitoring Center; Rachel Brody from the Biorepository and Pathology CoRE; and Fadi El Salem in the Department of Pathology at the Icahn School of Medicine for their technical assistance and guidance in experimental design. This research was supported by National Institute of Allergy and Infectious Diseases grants R01AI127372 , R21 AI134366 , and R21AI129827 ; the March of Dimes (to D.B.); and the Genetic Disease Foundation (to B.D.G.). This study was also funded by R01AI137275 to E.M.M., R01AI120989 to J.S.O., and R03DK117218 to D.D. Research in the Rosenberg laboratory was supported by DP5 OD012142 . J.C.M. was supported by “Prix pour les jeunes chercheurs” de la Fondation Bettencourt-Schueller and by the Philippe Foundation . C.N.G. was supported by T32 training grant 5T32HD075735-07 . J.J.A.C. was supported by the Netherlands Organization for Scientific Research (NWO Rubicon). Funding Information: We thank Adeeb Rahman, Brian Lee, Kevin Tuballes, and Laura Walker from the Human Immune Monitoring Center; Rachel Brody from the Biorepository and Pathology CoRE; and Fadi El Salem in the Department of Pathology at the Icahn School of Medicine for their technical assistance and guidance in experimental design. This research was supported by National Institute of Allergy and Infectious Diseases grants R01AI127372, R21 AI134366, and R21AI129827; the March of Dimes (to D.B.); and the Genetic Disease Foundation (to B.D.G.). This study was also funded by R01AI137275 to E.M.M. R01AI120989 to J.S.O. and R03DK117218 to D.D. Research in the Rosenberg laboratory was supported by DP5 OD012142. J.C.M. was supported by “Prix pour les jeunes chercheurs” de la Fondation Bettencourt-Schueller and by the Philippe Foundation. C.N.G. was supported by T32 training grant 5T32HD075735-07. J.J.A.C. was supported by the Netherlands Organization for Scientific Research (NWO Rubicon). C.N.G. designed and performed most of the experiments, analyzed the data, and wrote the manuscript. J.J.A.C. analyzed all of the scRNA-seq data and edited the manuscript. S.B. generated the cell lines and processed the whole-blood experiments. G.E. analyzed the sequencing data, performed ddPCR, and edited the manuscript. J.C.M. performed the tissue processing for ddPCR. S.A.U. and R.C. carried out the custom scRNA-seq experiments. E.M.M. and J.S.O. performed the NK cell experiments and analysis. L.J. D.D. R.P. and J.M.S. performed the clinical analyses and reports. B.R.R. designed the custom scRNA-seq, analyzed the data, and edited the manuscript. B.D.W. M.M. J.S.O. and B.D.G. helped to design the experiments and analyze the data. D.B. helped to design the experiments and analyze the data, supervised the work, and wrote the manuscript. All of the authors commented on the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = sep,
day = "15",
doi = "10.1016/j.immuni.2020.07.006",
language = "English",
volume = "53",
pages = "672--684.e11",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}