ArticleScience immunology2022
Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Acquired nonpermissive BM microenvironment impairs HSC proliferation and maintenance, and B-cell development after HSCT.Blood advances · 2026Article
- Case Report: Functional characterization of lymphocyte populations in a pediatric patient with WHIM syndrome.Frontiers in immunology · 2026Article
- Pancreatic hypersecretion of amyloid-forming human amylin dysregulates the neuro-immune axis and B cell development in a model of type-2 diabetes.Neurobiology of disease · 2025Article
- Bone marrow mesenchymal stroma cell serves as a harbor anchoring acute B lymphoblastic leukemia cells.Genes & diseases · 2025Article
- Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system.The Journal of experimental medicine · 2025Article
- CXCR4 antagonism corrects neutrophil abnormalities and reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia.Frontiers in immunology · 2025Article
- CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism.Science signaling · 2024Article
- Periodontal disease in patients with WHIM syndrome.Journal of clinical periodontology · 2024Article
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- CXCR4 antagonism ameliorates leukocyte abnormalities in a preclinical model of WHIM syndrome.Frontiers in immunology · 2024Article
- Article
- Severe CD8+ T Lymphopenia in WHIM Syndrome Caused by Selective Sequestration in Primary Immune Organs.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- WHIM Syndrome-linked CXCR4 mutations drive osteoporosis.Nature communications · 2023Article
- Mature B cells and mesenchymal stem cells control emergency myelopoiesis.Life science alliance · 2023Article
- Article
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Gain-of-function (GOF) mutations in CXCR4 cause WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, characterized by infections, leukocyte retention in bone marrow (BM), and blood leukopenias. B lymphopenia is evident at early progenitor stages, yet why do CXCR4 GOF mutations that cause B (and T) lymphopenia remain obscure? Using a CXCR4 R334X GOF mouse model of WHIM syndrome, we showed that lymphopoiesis is reduced because of a dysregulated mesenchymal stem cell (MSC) transcriptome characterized by a switch from an adipogenic to an osteolineage-prone program with limited lymphopoietic activity. We identify lymphotoxin beta receptor (LTβR) as a critical pathway promoting interleukin-7 (IL-7) down-regulation in MSCs. Blocking LTβR or CXCR4 signaling restored IL-7 production and B cell development in WHIM mice. LTβR blocking also increased production of IL-7 and B cell activating factor (BAFF) in secondary lymphoid organs (SLOs), increasing B and T cell numbers in the periphery. These studies revealed that LTβR signaling in BM MSCs and SLO stromal cells limits the lymphocyte compartment size.
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