Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy

Bousfiha, 2020, Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification, J. Clin. Immunol., 40, 66, 10.1007/s10875-020-00758-x Tangye, 2020, Human inborn errors of immunity: 2019 update on the classification from the international union of immunological societies expert committee, J. Clin. Immunol., 40, 24, 10.1007/s10875-019-00737-x Roos, 2017, Biochemical and genetic diagnosis of chronic granulomatous disease. Immunology and immune system disorders, 231 Roos, 2016, Chronic granulomatous disease, Br. Med. Bull., 118, 50, 10.1093/bmb/ldw009 van den Berg, 2009, Chronic granulomatous disease: the European experience, PLoS One, 4, e5234, 10.1371/journal.pone.0005234 Marciano, 2015, Common severe infections in chronic granulomatous disease, Clin. Infect. Dis., 60, 1176, 10.1093/cid/ciu1154 Magnani, 2014, Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease, J. Allergy Clin. Immunol., 134, 655, 10.1016/j.jaci.2014.04.014 Marciano, 2017, Inflammatory manifestations in chronic granulomatous disease, 163 van de Veerdonk, 2017, Dysfunctional processes regulating IL-1B in chronic granulomatous disease, 69–87, 69 Chiesa, 2020, Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults, Blood, 136, 1201, 10.1182/blood.2020005590 Cole, 2013, Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation, J. Allergy Clin. Immunol., 132, 1150, 10.1016/j.jaci.2013.05.031 Gennery, 2010, Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better?, J. Allergy Clin. Immunol., 126, 602, 10.1016/j.jaci.2010.06.015 Martinez, 2012, Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease, J. Allergy Clin. Immunol., 129, 176, 10.1016/j.jaci.2011.10.005 Grez, 2011, Gene therapy of chronic granulomatous disease: the engraftment dilemma, Mol. Ther., 19, 28, 10.1038/mt.2010.232 Malech, 1997, Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease, Proc. Natl. Acad. Sci. USA, 94, 12133, 10.1073/pnas.94.22.12133 Ott, 2006, Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1, Nat. Med., 12, 401, 10.1038/nm1393 Stein, 2010, Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease, Nat. Med., 16, 198, 10.1038/nm.2088 Brendel, 2018, Non-clinical efficacy and safety studies on G1XCGD, a lentiviral vector for ex vivo gene therapy of X-linked chronic granulomatous disease, Hum. Gene Ther. Clin. Dev., 29, 69, 10.1089/humc.2017.245 Kohn, 2020, Lentiviral gene therapy for X-linked chronic granulomatous disease, Nat. Med., 26, 200, 10.1038/s41591-019-0735-5 Weisser, 2016, Hyperinflammation in patients with chronic granulomatous disease leads to impairment of hematopoietic stem cell functions, J. Allergy Clin. Immunol., 138, 219, 10.1016/j.jaci.2015.11.028 Meda Spaccamela, 2019, High levels of IL-18 and IFN-γ in chronically inflamed tissue in chronic granulomatous disease, Front. Immunol., 10, 2236, 10.3389/fimmu.2019.02236 Zonari, 2017, Efficient ex vivo engineering and expansion of highly purified human hematopoietic stem and progenitor cell populations for gene therapy, Stem Cell Rep., 8, 977, 10.1016/j.stemcr.2017.02.010 Martignetti, 2016, ROMA: representation and quantification of module activity from target expression data, Front. Genet., 7, 18, 10.3389/fgene.2016.00018 Kiselev, 2019, Challenges in unsupervised clustering of single-cell RNA-seq data, Nat. Rev. Genet., 20, 273, 10.1038/s41576-018-0088-9 Cortal, 2021, Gene signature extraction and cell identity recognition at the single-cell level with Cell-ID, Nat. Biotechnol., 39, 1095, 10.1038/s41587-021-00896-6 Velten, 2017, Human haematopoietic stem cell lineage commitment is a continuous process, Nat. Cell Biol., 19, 271, 10.1038/ncb3493 Finak, 2015, MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data, Genome Biol., 16, 278, 10.1186/s13059-015-0844-5 Liberzon, 2015, The Molecular Signatures Database (MSigDB) hallmark gene set collection, Cell Syst., 1, 417, 10.1016/j.cels.2015.12.004 Torang, 2019, An elastic-net logistic regression approach to generate classifiers and gene signatures for types of immune cells and T helper cell subsets, BMC Bioinf., 20, 433, 10.1186/s12859-019-2994-z Pietras, 2016, Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal, Nat. Cell Biol., 18, 607, 10.1038/ncb3346 Chen, 2010, Mammalian target of rapamycin activation underlies HSC defects in autoimmune disease and inflammation in mice, J. Clin. Invest., 120, 4091, 10.1172/JCI43873 Takizawa, 2017, Pathogen-induced TLR4-TRIF innate immune signaling in hematopoietic stem cells promotes proliferation but reduces competitive fitness, Cell Stem Cell, 21, 225, 10.1016/j.stem.2017.06.013 Zhang, 2016, Sepsis induces hematopoietic stem cell exhaustion and myelosuppression through distinct contributions of TRIF and MYD88, Stem Cell Rep., 6, 940, 10.1016/j.stemcr.2016.05.002 Hirai, 2006, C/EBPbeta is required for “emergency” granulopoiesis, Nat. Immunol., 7, 732, 10.1038/ni1354 Manz, 2014, Emergency granulopoiesis, Nat. Rev. Immunol., 14, 302, 10.1038/nri3660 Montandon, 2013, Innate pro-B-cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells, Proc. Natl. Acad. Sci. USA, 110, E2199, 10.1073/pnas.1222446110 Xie, 2004, Stepwise reprogramming of B cells into macrophages, Cell, 117, 663, 10.1016/S0092-8674(04)00419-2 Audzevich, 2017, Pre/pro-B cells generate macrophage populations during homeostasis and inflammation, Proc. Natl. Acad. Sci. USA, 114, E3954, 10.1073/pnas.1616417114 Essers, 2009, IFNalpha activates dormant haematopoietic stem cells in vivo, Nature, 458, 904, 10.1038/nature07815 Matatall, 2016, Chronic infection depletes hematopoietic stem cells through stress-induced terminal differentiation, Cell Rep., 17, 2584, 10.1016/j.celrep.2016.11.031 King, 2011, Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling, Blood, 118, 1525, 10.1182/blood-2011-01-328682 Sato, 2009, Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion, Nat. Med., 15, 696, 10.1038/nm.1973 Lin, 2014, IFN-γ causes aplastic anemia by altering hematopoietic stem/progenitor cell composition and disrupting lineage differentiation, Blood, 124, 3699, 10.1182/blood-2014-01-549527 Baldridge, 2010, Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection, Nature, 465, 793, 10.1038/nature09135 Crow, 2022, The type I interferonopathies: 10 years on, Nat. Rev. Immunol., 22, 471, 10.1038/s41577-021-00633-9 Roy, 2021, Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development, Cell Rep., 36, 109698, 10.1016/j.celrep.2021.109698 Lu, 2022, Srebf1c preserves hematopoietic stem cell function and survival as a switch of mitochondrial metabolism, Stem Cell Rep., 17, 599, 10.1016/j.stemcr.2022.01.011 de Laval, 2020, C/EBPβ-Dependent epigenetic memory induces trained immunity in hematopoietic stem cells, Cell Stem Cell, 26, 793, 10.1016/j.stem.2020.03.014 Esplin, 2011, Chronic exposure to a TLR ligand injures hematopoietic stem cells, J. Immunol., 186, 5367, 10.4049/jimmunol.1003438 Davidsson, 2018, SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies, Leukemia, 32, 1106, 10.1038/s41375-018-0074-4 Thomas, 2021, Pediatric MDS and bone marrow failure-associated germline mutations in SAMD9 and SAMD9L impair multiple pathways in primary hematopoietic cells, Leukemia, 35, 3232, 10.1038/s41375-021-01212-6 Hoggatt, 2009, Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation, Blood, 113, 5444, 10.1182/blood-2009-01-201335 North, 2007, Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis, Nature, 447, 1007, 10.1038/nature05883 Chace, 1995, Regulation of differentiation of peritoneal B-1a (CD5+) B cells. Activated peritoneal macrophages release prostaglandin E2, which inhibits IgM secretion by peritoneal B-1a cells, J. Immunol., 154, 5630, 10.4049/jimmunol.154.11.5630 Weissmann, 1993, Prostaglandins as modulators rather than mediators of inflammation, J. Lipid Mediat., 6, 275 Goujon, 2013, Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection, Nature, 502, 559, 10.1038/nature12542 Colomer-Lluch, 2018, Restriction factors: from intrinsic viral restriction to shaping cellular immunity against HIV-1, Front. Immunol., 9, 2876, 10.3389/fimmu.2018.02876 Petrillo, 2018, Cyclosporine H overcomes innate immune restrictions to improve lentiviral transduction and gene editing in human hematopoietic stem cells, Cell Stem Cell, 23, 820, 10.1016/j.stem.2018.10.008 Jofra Hernández, 2021, Hematopoietic tumors in a mouse model of X-linked chronic granulomatous disease after lentiviral vector-mediated gene therapy, Mol. Ther., 29, 86, 10.1016/j.ymthe.2020.09.030 Klatt, 2020, Competitive sgRNA screen identifies p38 MAPK as a druggable target to improve HSPC engraftment, Cells, 9, 2194, 10.3390/cells9102194 Vanderver, 2020, Janus kinase inhibition in the aicardi-goutières syndrome, N. Engl. J. Med., 383, 986, 10.1056/NEJMc2001362 Sanchez, 2018, JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies, J. Clin. Invest., 128, 3041, 10.1172/JCI98814 Forbes, 2018, Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations, J. Allergy Clin. Immunol., 142, 1665, 10.1016/j.jaci.2018.07.020 Schuettpelz, 2014, G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling, Leukemia, 28, 1851, 10.1038/leu.2014.68 Walter, 2015, Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells, Nature, 520, 549, 10.1038/nature14131 Schmidt, 2001, Detection and direct genomic sequencing of multiple rare unknown flanking DNA in highly complex samples, Hum. Gene Ther., 12, 743, 10.1089/104303401750148649 Afzal, 2017, GENE-IS: time-efficient and accurate analysis of viral integration events in large-scale gene therapy data, Mol. Ther. Nucleic Acids, 6, 133, 10.1016/j.omtn.2016.12.001 Love, 2014, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol., 15, 550, 10.1186/s13059-014-0550-8 Subramanian, 2005, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc. Natl. Acad. Sci. USA, 102, 15545, 10.1073/pnas.0506580102 Lun, 2016, Pooling across cells to normalize single-cell RNA sequencing data with many zero counts, Genome Biol., 17, 75, 10.1186/s13059-016-0947-7 Couckuyt, 2022, Challenges in translational machine learning, Hum. Genet., 141, 1451, 10.1007/s00439-022-02439-8 Zou, 2005, Regularization and variable selection via the elastic net, J. Roy. Stat. Soc. B, 67, 301, 10.1111/j.1467-9868.2005.00503.x