We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling.
- Authors
Nunes-Santos, Cristiane J.; Kuehn, HyeSun; Boast, Brigette; Hwang, SuJin; Kuhns, Douglas B.; Stoddard, Jennifer; Niemela, Julie E.; Fink, Danielle L.; Pittaluga, Stefania; Abu-Asab, Mones; Davies, John S.; Barr, Valarie A.; Kawai, Tomoki; Delmonte, Ottavia M.; Bosticardo, Marita; Garofalo, Mary; Carneiro-Sampaio, Magda; Somech, Raz; Gharagozlou, Mohammad; Parvaneh, Nima
- 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. Mutations that impact the function of the Arp2/3 complex are known to cause inborn errors of immunity. Here the authors describe biallelic null mutations in the ARPC5 subunit of Arp2/3 that disrupt actin function and cytokine signaling, causing infections, autoimmunity, inflammation and dysmorphisms.
- Subjects
CYTOKINES; GENETIC mutation; PROTEIN expression; CELL physiology; DISEASE relapse; INTERLEUKIN-23
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39272-0