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

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.

 Fuente: Cell Death Discovery, 2022, 8(1), 316

 Editorial: Springer Nature

 Año de publicación: 2022

 Nº de páginas: 11

 Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41420-022-01115-0

 ISSN: 2058-7716

Autoría

SERRANO-MACIÁ, MARINA

LACHIONDO-ORTEGA, LUCÍA

IRUZUBIETA, PAULA

GOIKOETXEA-USANDIZAGA, NAROA

BOSCH, ALEXANDRE

EGIA-MENDIKUTE, LEIRE

JIMÉNEZ-LASHERAS, BORJA

AZKARGORTA, MIKEL

ELORTZA, FÉLIX

MARTÍNEZ-REDONDO, DIANA

CASTRO, BEGOÑA

LOZANO, JUAN J.

NOGUEIRAS, RUBÉN

JUAN IRURE VENTURA

CRESPO, JAVIER

PALAZÓN, ASÍS

MARTÍNEZ-CHANTAR, MARÍA L.