ArticlePLoS medicine2008
IFN-gamma mediates the rejection of haematopoietic stem cells in IFN-gammaR1-deficient hosts.
Article in PLoS medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review.The Journal of allergy and clinical immunology · 2024Pooled it
- An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China.Frontiers in immunology · 2022Pooled it
- Successful Hematopoietic Stem Cell Transplantation in a Patient with Complete IFN-γ Receptor 2 Deficiency: a Case Report and Literature Review.Journal of clinical immunology · 2020Pooled it
- How I Treat: Transplantation for primary immune regulatory diseases and inflammatory disorders.Journal of human immunity · 2026Article
- Tailored conditioning for hematopoietic stem cell transplantation in children with Mendelian susceptibility to mycobacterial disease: A tale of two pathways for IFN-γ and IL-12 defects.Journal of human immunity · 2026Article
- Adult Onset of MSMD Caused by IL-12Rβ1 Variants: Report of a Young Woman with NTM Infection Lacking Bacille Calmette-Guérin (BCG)-induced Diseases.Journal of clinical immunology · 2026Article
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- Emapalumab for the Treatment of Immune-Mediated Graft Failure after HSCT.Bone marrow transplantation · 2025Article
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- Low dose post-transplant cyclophosphamide and sirolimus induce mixed chimerism with CTLA4-Ig or lymphocyte depletion in an MHC-mismatched murine allotransplantation model.Bone marrow transplantation · 2024Article
- A Novel Combination of Compound Heterozygous Variants in IFNGR1 Causing Complete IFNGR1 Deficiency.Journal of clinical immunology · 2024Article
- Interferon-Science (New York, N.Y.) · 2024Review
- Diagnosis and Management of Infections in Patients with Mendelian Susceptibility to Mycobacterial Disease.Pathogens (Basel, Switzerland) · 2024Review
- Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2.Nature communications · 2023Article
- Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases.Journal of fungi (Basel, Switzerland) · 2023Review
- Combined use of emapalumab and ruxolitinib in a patient with refractory hemophagocytic lymphohistiocytosis was safe and effective.Pediatric blood & cancer · 2021Article
- The Use of Biologic Modifiers as a Bridge to Hematopoietic Cell Transplantation in Primary Immune Regulatory Disorders.Frontiers in immunology · 2021Review
- Promoting effect of long non-coding RNA SNHG1 on osteogenic differentiation of fibroblastic cells from the posterior longitudinal ligament by the microRNA-320b/IFNGR1 network.Cell cycle (Georgetown, Tex.) · 2020Article
- DisseminatedJournal of pediatric genetics · 2020Article
- Human Lentiviral Gene Therapy Restores the Cellular Phenotype of Autosomal Recessive Complete IFN-γR1 Deficiency.Molecular therapy. Methods & clinical development · 2020Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterferon-gamma receptor 1 (IFN-gammaR1) deficiency is a life-threatening inherited disorder, conferring predisposition to mycobacterial diseases. Haematopoietic stem cell transplantation (HSCT) is the only curative treatment available, but is hampered by a very high rate of graft rejection, even with intra-familial HLA-identical transplants. This high rejection rate is not seen in any other congenital disorders and remains unexplained. We studied the underlying mechanism in a mouse model of HSCT for IFN-gammaR1 deficiency. METHODS AND
findingsWe demonstrated that HSCT with cells from a syngenic C57BL/6 Ifngr1+/+ donor engrafted well and restored anti-mycobacterial immunity in naive, non-infected C57BL/6 Ifngr1-/- recipients. However, Ifngr1-/- mice previously infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) rejected HSCT. Like infected IFN-gammaR1-deficient humans, infected Ifngr1-/- mice displayed very high serum IFN-gamma levels before HSCT. The administration of a recombinant IFN-gamma-expressing AAV vector to Ifngr1-/- naive recipients also resulted in HSCT graft rejection. Transplantation was successful in Ifngr1-/- x Ifng-/- double-mutant mice, even after BCG infection. Finally, efficient antibody-mediated IFN-gamma depletion in infected Ifngr1-/- mice in vivo allowed subsequent engraftment.
conclusionsHigh serum IFN-gamma concentration is both necessary and sufficient for graft rejection in IFN-gammaR1-deficient mice, inhibiting the development of heterologous, IFN-gammaR1-expressing, haematopoietic cell lineages. These results confirm that IFN-gamma is an anti-haematopoietic cytokine in vivo. They also pave the way for HSCT management in IFN-gammaR1-deficient patients through IFN-gamma depletion from the blood. They further raise the possibility that depleting IFN-gamma may improve engraftment in other settings, such as HSCT from a haplo-identical or unrelated donor.
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