2. Academic Validation
  3. Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients

Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients

  • Cell Death Discov. 2022 Jul 12;8(1):316. doi: 10.1038/s41420-022-01115-0.
Marina Serrano-Maciá  # 1,  Sofia Lachiondo-Ortega  # 1,  Paula Iruzubieta 2,  Naroa Goikoetxea-Usandizaga 1,  Alexandre Bosch 3,  Leire Egia-Mendikute 3,  Borja Jiménez-Lasheras 3,  Mikel Azkargorta 4,  Félix Elortza 4,  Diana Martinez-Redondo 5,  Begoña Castro 5,  Juan J Lozano 6,  Ruben Nogueiras 7 8 9,  Juan Irure-Ventura 10,  Javier Crespo 2,  Asís Palazón 3 11,  María Carmen Fariñas 12,  Teresa C Delgado 1,  Marcos López-Hoyos 10,  Maria L Martínez-Chantar 13
Affiliations

Affiliations

  • 1 Liver Disease Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
  • 2 Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, Santander, Spain.
  • 3 Cancer Immunology and Immunotherapy Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia, Spain.
  • 4 Proteomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Carlos IIINetworked Proteomics Platform (ProteoRed-ISCIII), 48160, Derio, Bizkaia, Spain.
  • 5 Histocell S.L., Bizkaia Science and Technology Park, Derio, Bizkaia, Spain.
  • 6 Bioinformatics Platform, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain.
  • 7 Department of Physiology, Research Centre of Molecular Medicine and Chronic Diseases, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
  • 8 Centro de Fisiopatología de la Obesidad y Nutrición, Centro de Investigación Biomédica en Red, Santiago de Compostela, Spain.
  • 9 Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, Spain.
  • 10 Servicio Inmunología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Facultad de Medicina, Universidad de Cantabria, Barcelona, Cantabria, Spain.
  • 11 Ikerbasque, Basque Foundation for Science, Bizkaia, Spain.
  • 12 Servicio Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla-IDIVAL, Facultad de Medicina, Universidad de Cantabria, Barcelona, Cantabria, Spain.
  • 13 Liver Disease Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain. mlmartinez@cicbiogune.es.
  • # Contributed equally.
PMID: 35831294 DOI: 10.1038/s41420-022-01115-0
Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral Infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the activation of the immune system and its implications in viral Infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in COVID-19 in the serum of patients, which is particularly associated with the early response to Infection. In addition, the results showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential approach to immunomodulate COVID-19 patients.

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