Unraveling the role of macrophages in regulating inflammatory lipids during acute kidney injury

Tsukuba, Japan—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 and play a pivotal role in promoting and suppressing inflammation. Thus, elucidating their function is of paramount importance.

In this study, 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.

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The research was conducted as part of research projects funded by JSPS KAKENHI (Grants 19K07499 and 23K05586), the Strategic Basic Research Programs (JPMJPF2017), and the Program for Next Generation Researchers Challenging Research (JPMJSP2124).

_{Original Paper}

Title of original paper:
MAFB in macrophages regulates PGE2-mediated lipid mediator class switch through ALOX15 in ischemic Acute Kidney Injury

Journal:
The Journal of Immunology

DOI:
10.4049/jimmunol.2300844

_{Correspondence}

Associate Professor HAMADA, Michito
Institute of Medicine, University of Tsukuba

_{Related Link}

Institute of Medicine