Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling

Cristiane J. Nunes-Santos, HyeSun Kuehn, Brigette Boast, SuJin Hwang, Douglas B. Kuhns, Jennifer Stoddard, Julie E. Niemela, Danielle L. Fink, Stefania Pittaluga, Mones Abu-Asab, John S. Davies, Valarie A. Barr, Tomoki Kawai, Ottavia M. Delmonte, Marita Bosticardo, Mary Garofalo, Magda Carneiro-Sampaio, Raz Somech, Mohammad Gharagozlou, Nima Parvaneh, Lawrence E. Samelson, Thomas A. Fleisher, Anne Puel, Luigi D. Notarangelo, Bertrand Boisson, Jean-Laurent Casanova, Beata Derfalvi and Sergio D. Rosenzweig ()
Additional contact information
Cristiane J. Nunes-Santos: National Institutes of Health
HyeSun Kuehn: National Institutes of Health
Brigette Boast: National Institutes of Health
SuJin Hwang: National Institutes of Health
Douglas B. Kuhns: Frederick National Laboratory for Cancer Research
Jennifer Stoddard: National Institutes of Health
Julie E. Niemela: National Institutes of Health
Danielle L. Fink: Frederick National Laboratory for Cancer Research
Stefania Pittaluga: National Institutes of Health
Mones Abu-Asab: National Institutes of Health
John S. Davies: Predictive Toxicology Department of Safety Assessment, Genentech
Valarie A. Barr: National Institutes of Health
Tomoki Kawai: National Institutes of Health
Ottavia M. Delmonte: National Institutes of Health
Marita Bosticardo: National Institutes of Health
Mary Garofalo: National Institutes of Health
Magda Carneiro-Sampaio: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
Raz Somech: Edmond and Lily Safra Children’s Hospital
Mohammad Gharagozlou: University of Medical Sciences
Nima Parvaneh: University of Medical Sciences
Lawrence E. Samelson: National Institutes of Health
Thomas A. Fleisher: National Institutes of Health
Anne Puel: The Rockefeller University
Luigi D. Notarangelo: National Institutes of Health
Bertrand Boisson: The Rockefeller University
Jean-Laurent Casanova: The Rockefeller University
Beata Derfalvi: Dalhousie University and IWK Health Center
Sergio D. Rosenzweig: National Institutes of Health

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)−6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39272-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39272-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39272-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().