Work

Dual Immunomodulatory Roles of MARCKS in Proinflammatory and Type I Interferon Signaling in Macrophages 2306298

Year: 2026

Type: article

Abstract: Introduction Lipopolysaccharide (LPS) signaling plays a critical role in innate immune responses and inflammation. Myristoylated alanine-rich C-kinase substrate (MARCKS) has been implicated in various signaling pathways; however, its immunomodulatory mechanisms remain unclear. In this study, we used proteogenomic analysis to investigate the function of MARCKS in the LPS response. Unexpectedly, our results revealed that MARCKS acts as both a positive and negative regulator of LPS signaling, suggesting a reciprocal role of MARCKS. This dual role challenges the current understanding of MARCKS function. In macrophages, loss of MARCKS resulted in reduced inflammation, marked by decreased TNF-induced amplification and attenuated activation of NF-κB and MAPK pathways. In contrast, MARCKS deficiency enhanced interferon signaling, with elevated IFN-β production and upregulation of interferon-stimulated genes (ISGs) via the JAK-STAT pathway. These findings reveal a previously unrecognized dual function of MARCKS in modulating both inflammatory and interferon responses, with implications for targeting immune dysregulation in disease Methods Results Conclusion Funding Source This research was supported by the Intramural Research Program of NIAID, NIH. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkag141.1326

Authors: Jiraphorn Issara-Amphorn, Aleksandra Nita-Lazar

Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases

Language: English

Topic: Immune Response and Inflammation

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W7171563581