by University of Tsukuba

RNA-seq analysis on macrophages isolated from the kidney of Mafb^f/f and Mafb^f/f::LysM-Cre mice 24 h post-IRI. Credit: The Journal of Immunology (2024). DOI: 10.4049/jimmunol.2300844

Acute kidney injury (AKI) is associated with a poor prognosis, and no effective treatment has been established to date. Understanding the mechanisms that prevent the progression of AKI is crucial. In AKI, immune cells known as macrophages produce lipid mediators (LMs), which are lipids with significant physiological activity that play a pivotal role in promoting and suppressing inflammation. Thus, elucidating their function is of paramount importance.

In a new study published in The Journal of Immunology, researchers focused on the transcription factor MAFB that has been reported to regulate the inflammation-suppressive capacity of macrophages. They analyzed the function of macrophages in the context of AKI.

When AKI was induced in mice specifically lacking MAFB in macrophages (MAFB-deficient mice), the prognosis was worse compared to that of wild-type mice. A comprehensive analysis of gene expression in macrophages from the MAFB-deficient mice revealed a marked decrease in the expression of the gene ALOX15; ALOX15 is an enzyme essential for the production of pro-resolving LMs.

Furthermore, the expression of MAFB in macrophages during AKI is regulated by a pro-inflammatory lipid mediator known as PGE2, and MAFB regulates ALOX15 expression under the influence of PGE2. These findings collectively suggest that MAFB plays a critical role in shifting LMs from a pro-inflammatory to a pro-resolving state.

Given that the balance between pro-inflammatory and pro-resolving LMs significantly impacts the prognosis of acute inflammation, the results of this study are expected to contribute to the development of therapeutic and diagnostic methods for AKI and other acute inflammatory diseases.

More information: Maho Kanai et al, MAFB in Macrophages Regulates Prostaglandin E2–Mediated Lipid Mediator Class Switch through ALOX15 in Ischemic Acute Kidney Injury, The Journal of Immunology (2024). DOI: 10.4049/jimmunol.2300844

Journal information: Journal of Immunology 

Provided by University of Tsukuba