ArticleJCI insight2016
A cytotoxic anti-IL-3Rα antibody targets key cells and cytokines implicated in systemic lupus erythematosus.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave's disease and control.BMC molecular and cell biology · 2025Article
- From the bench to the clinic: basophils and type 2 epithelial cytokines of thymic stromal lymphopoietin and IL-33.Clinical & translational immunology · 2024Review
- Current perspective on biological properties of plasmacytoid dendritic cells and dysfunction in gut.Immunity, inflammation and disease · 2023Review
- CSL362 potently and specifically depletes pDCsiScience · 2023Article
- Emerging concepts of type I interferons in SLE pathogenesis and therapy.Nature reviews. Rheumatology · 2022Review
- Hydroxychloroquine inhibits the mitochondrial antioxidant system in activated T cells.iScience · 2021Article
- Behind the scenes with basophils: an emerging therapeutic target.Immunotherapy advances · 2021Review
- IgE in the Pathogenesis of SLE: From Pathogenic Role to Therapeutic Target.Antibodies (Basel, Switzerland) · 2020Review
- Platelets and IgE: Shaping the Innate Immune Response in Systemic Lupus Erythematosus.Clinical reviews in allergy & immunology · 2020Review
- Review
- Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus.Clinical & translational immunology · 2019Article
- A potential association between IL-3 and type I and III interferons in systemic lupus erythematosus.Clinical & translational immunology · 2019Article
- Role of the β Common (βc) Family of Cytokines in Health and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.Nature communications · 2018Article
- TANK-Binding Kinase 1-Dependent Responses in Health and Autoimmunity.Frontiers in immunology · 2018Review
- Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases.Nature reviews. Drug discovery · 2016Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, the major target of biologic therapeutics in systemic lupus erythematosus (SLE) has been the B cell, which produces pathogenic autoantibodies. Recently, targeting type I IFN, which is elaborated by plasmacytoid dendritic cells (pDCs) in response to endosomal TLR7 and TLR9 stimulation by SLE immune complexes, has shown promising results. pDCs express high levels of the IL-3Rα chain (CD123), suggesting an alternative potential targeting strategy. We have developed an anti-CD123 monoclonal antibody, CSL362, and show here that it affects key cell types and cytokines that contribute to SLE. CSL362 potently depletes pDCs via antibody-dependent cell-mediated cytotoxicity, markedly reducing TLR7, TLR9, and SLE serum-induced IFN-α production and IFN-α-upregulated gene expression. The antibody also inhibits TLR7- and TLR9-induced plasmablast expansion by reducing IFN-α and IL-6 production. These effects are more pronounced than with IFN-α blockade alone, possibly because pDC depletion reduces production of other IFN subtypes, such as type III, as well as non-IFN proinflammatory cytokines, such as IL-6. In addition, CSL362 depletes basophils and inhibits IL-3 signaling. These effects were confirmed in cells derived from a heterogeneous population of SLE donors, various IFN-dependent autoimmune diseases, and healthy controls. We also demonstrate in vivo activity of CSL362 following its s.c. administration to cynomolgus monkeys. This spectrum of effects provides a preclinical rationale for the therapeutic evaluation of CSL362 in SLE.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.