학술논문
Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling
Document Type
article
Author
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; Sergio D. Rosenzweig
Source
Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023)
Subject
Language
English
ISSN
2041-1723
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.