@article{539c4c71456e449bb4ec84bc6668538a,
title = "CSL362 potently and specifically depletes pDCs in vitro and ablates SLE-immune complex-induced IFN responses",
abstract = "Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity and mortality. Type I interferon (IFN) drives SLE pathology and plasmacytoid dendritic cells (pDCs) are potent producers of IFN; however, the specific effects of pDC depletion have not been demonstrated. We show CD123 was highly expressed on pDCs and the anti-CD123 antibody CSL362 potently depleted pDCs in vitro. CSL362 pre-treatment abrogated the induction of IFNα and IFN-induced gene transcription following stimulation with SLE patient-derived serum or immune complexes. RNA transcripts induced in pDCs by ex vivo stimulation with TLR ligands were reflected in gene expression profiles of SLE blood, and correlated with disease severity. TLR ligand-induced protein production by SLE patient peripheral mononuclear cells was abrogated by CSL362 pre-treatment including proteins over expressed in SLE patient serum. These findings implicate pDCs as key drivers in the cellular activation and production of soluble factors seen in SLE.",
keywords = "Health sciences, Immunology, Pathophysiology",
author = "Monaghan, {Katherine A.} and Alberta Hoi and Cristina Gamell and Tai, {Tsin Yee} and Bryan Linggi and Jarrat Jordan and Matteo Cesaroni and Takahiro Sato and Milica Ng and Shereen Oon and Jacqueline Benson and Ian Wicks and Eric Morand and Nicholas Wilson",
note = "Funding Information: Susan Morton and Rachel Koelmeyer for sample collection and the clinical database. Catherine Tarlinton for FACS sorting of pDCs. Jessica Schreiter for the immune complexes. All the blood donors. The Australian Genome Research Facility for the RNA-seq. Gino Vairo for project support. Derchieh Hung for assistance with statistical analysis. Mark Biondo for assistance with RNA extractions. IW{\textquoteright}s work was supported by Australian National Health and Medical Research Council (NHMRC) Program Grant 1023407 (IW) and Clinical Practitioner Fellowship 1154325 (IW). This study was made possible through Victorian State Government Operational Infrastructure Support and the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support scheme (IW). IW{\textquoteright}s laboratory is also supported by the Reid Charitable Trusts . Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = jul,
day = "21",
doi = "10.1016/j.isci.2023.107173",
language = "English",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "7",
}