ArticleNature immunology2023
G-CSF drives autoinflammation in APLAID.
Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- CSF2 drives radiation-induced lung injury by eliciting PADI4-high pathogenic neutrophils.Journal of translational medicine · 2026Article
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Overlap of familial Mediterranean fever and APLAID treated with anakinra: a case-based review.Clinical rheumatology · 2025Review
- Early-onset bibasilar emphysema in a patient with PLCG2-related immune dysregulation.Respiratory medicine case reports · 2025Article
- The human plasma anellome exhibits age- and sex-dependent patterns with links to cardiometabolic health in older adults.Frontiers in microbiology · 2025Article
- APLAID complicated with arrhythmogenic dilated cardiomyopathy caused by a novel PLCG2 variant.Immunologic research · 2024Article
- PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.The Journal of allergy and clinical immunology · 2024Article
- Mind bomb 2 limits inflammatory dermatitis inPNAS nexus · 2024Article
- A gain-of-function variation in PLCG1 causes a new immune dysregulation disease.The Journal of allergy and clinical immunology · 2023Article
- G-CSF implicated as therapeutic target in APLAID.Nature reviews. Rheumatology · 2023Article
- The autoinflammatory disease APLAID is driven by G-CSF.Nature reviews. Immunology · 2023Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Missense mutations in PLCG2 can cause autoinflammation with phospholipase C gamma 2-associated antibody deficiency and immune dysregulation (APLAID). Here, we generated a mouse model carrying an APLAID mutation (p.Ser707Tyr) and found that inflammatory infiltrates in the skin and lungs were only partially ameliorated by removing inflammasome function via the deletion of caspase-1. Also, deleting interleukin-6 or tumor necrosis factor did not fully prevent APLAID mutant mice from autoinflammation. Overall, these findings are in accordance with the poor response individuals with APLAID have to treatments that block interleukin-1, JAK1/2 or tumor necrosis factor. Cytokine analysis revealed increased granulocyte colony-stimulating factor (G-CSF) levels as the most distinct feature in mice and individuals with APLAID. Remarkably, treatment with a G-CSF antibody completely reversed established disease in APLAID mice. Furthermore, excessive myelopoiesis was normalized and lymphocyte numbers rebounded. APLAID mice were also fully rescued by bone marrow transplantation from healthy donors, associated with reduced G-CSF production, predominantly from non-hematopoietic cells. In summary, we identify APLAID as a G-CSF-driven autoinflammatory disease, for which targeted therapy is feasible.
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