Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling

Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling Publisher Pubmed

Nunessantos CJ¹ ; Kuehn HS¹ ; Boast B¹ ; Hwang SJ¹ ; Kuhns DB² ; Stoddard J¹ ; Niemela JE¹ ; Fink DL² ; Pittaluga S³ ; Abuasab M⁴ ; Davies JS⁵ ; Barr VA⁶ ; Kawai T⁷ ; Delmonte OM⁷ Show All Authors

Nunessantos CJ¹
Kuehn HS¹
Boast B¹
Hwang SJ¹
Kuhns DB²
Stoddard J¹
Niemela JE¹
Fink DL²
Pittaluga S³
Abuasab M⁴
Davies JS⁵
Barr VA⁶
Kawai T⁷
Delmonte OM⁷
Bosticardo M⁷
Garofalo M⁸
Carneirosampaio M⁹
Somech R^{10, 11, 12}
Gharagozlou M¹³
Parvaneh N¹³
Samelson LE⁶
Fleisher TA¹
Puel A^{14, 15, 16}
Notarangelo LD⁷
Boisson B^{14, 15, 16}
Casanova JL^{14, 15, 16, 17, 18}
Derfalvi B¹⁹
Rosenzweig SD¹

Show Affiliations

1. Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States
2. Neutrophil Monitoring Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
3. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
4. Electron Microscopy Laboratory, Biological Imaging Core, National Eye Institute, National Institutes of Health, Bethesda, MD, United States
5. Predictive Toxicology Department of Safety Assessment, Genentech, South San Francisco, CA, United States
6. Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
7. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
8. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
9. Childrenâ€™s Hospital, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, Brazil
10. Pediatric Department A and Immunology Service, Edmond and Lily Safra Childrenâ€™s Hospital, Tel Hashomer, Israel
11. The Jeffrey Modell Foundation Israeli Network for Primary Immunodeficiency, New York, NY, United States
12. Sheba Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
13. Division of Allergy and Clinical Immunology, Department of Pediatrics, Childrenâ€™s Medical Centre, University of Medical Sciences, Tehran, Iran
14. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
15. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
16. Universite Paris Cite, Imagine Institute, Paris, France
17. Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France
18. Howard Hughes Medical Institute, New York, NY, United States
19. Department of Pediatrics, Division of Immunology, Dalhousie University and IWK Health Center, Halifax, NS, Canada

Source: Nature Communications Published:2023

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. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Style	Citing Format
MLA	Nunessantos CJ, et al.. "Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling." Nature Communications, vol. 14, no. 1, 2023, pp. -.
APA	Nunessantos CJ, Kuehn HS, Boast B, Hwang SJ, Kuhns DB, Stoddard J, Niemela JE, Fink DL, Pittaluga S, Abuasab M, Davies JS, Barr VA, Kawai T, Delmonte OM, Bosticardo M, Garofalo M, Carneirosampaio M, Somech R, Gharagozlou M, ... Rosenzweig SD (2023). Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling. Nature Communications, 14(1), -.
Chicago	Nunessantos CJ, Kuehn HS, Boast B, Hwang SJ, Kuhns DB, Stoddard J, Niemela JE, et al.. "Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling." Nature Communications 14, no. 1 (2023): -.
Harvard	Nunessantos CJ et al. (2023) 'Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling', Nature Communications, 14(1), pp. -.
Vancouver	Nunessantos CJ, Kuehn HS, Boast B, Hwang SJ, Kuhns DB, Stoddard J, et al.. Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling. Nature Communications. 2023;14(1):-.
BibTex	@article{ author = {Nunessantos CJ and Kuehn HS and Boast B and Hwang SJ and Kuhns DB and Stoddard J and Niemela JE and Fink DL and Pittaluga S and Abuasab M and Davies JS and Barr VA and Kawai T and Delmonte OM and Bosticardo M and Garofalo M and Carneirosampaio M and Somech R and Gharagozlou M and Parvaneh N and Samelson LE and Fleisher TA and Puel A and Notarangelo LD and Boisson B and Casanova JL and Derfalvi B and Rosenzweig SD}, title = {Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling}, journal = {Nature Communications}, volume = {14}, number = {1}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Nunessantos CJ AU - Kuehn HS AU - Boast B AU - Hwang SJ AU - Kuhns DB AU - Stoddard J AU - Niemela JE AU - Fink DL AU - Pittaluga S AU - Abuasab M AU - Davies JS AU - Barr VA AU - Kawai T AU - Delmonte OM AU - Bosticardo M AU - Garofalo M AU - Carneirosampaio M AU - Somech R AU - Gharagozlou M AU - Parvaneh N AU - Samelson LE AU - Fleisher TA AU - Puel A AU - Notarangelo LD AU - Boisson B AU - Casanova JL AU - Derfalvi B AU - Rosenzweig SD TI - Inherited Arpc5 Mutations Cause an Actinopathy Impairing Cell Motility and Disrupting Cytokine Signaling JO - Nature Communications VL - 14 IS - 1 SP - EP - PY - 2023 ER -

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