TY  - JOUR
T1  - Sustained Low-Level IFN-γ Drives Mitochondrial Complex I Dysfunction and Macrophage Dysregulation in Lupus Nephritis
A1  - Hiroshi Tanaka
A1  - Yuki Sato
A1  - Kenji Mori
A1  - Rina Okabe
A1  - Takashi Ito
JF  - Bulletin of Pioneering Researches of Medical and Clinical Science
JO  - Bull Pioneer Res Med Clin Sci
SN  - 3006-2659
Y1  - 2024
VL  - 4
IS  - 1
DO  - 10.51847/s1aAndrYLe
SP  - 201
EP  - 212
N2  - The pathogenesis of autoimmune conditions is known to be significantly influenced by both macrophage dysregulation and mitochondrial malfunction. Nevertheless, the precise pathways that couple these two elements remain inadequately defined. We propose in this study that a sustained, low-grade presence of interferon-gamma (IFN-γ) acts as a pivotal mediator in these events. To examine this, experiments were conducted using ARE-Del mice, a strain that displays enduring, low-level IFN-γ production alongside features characteristic of lupus nephritis (LN). Investigation of gene expression as a function of age and tissue type in these mice revealed pronounced downregulation of mitochondrial complex I subunits and their associated functions, particularly in renal tissue. The suppression of mitochondrial complex I linked to the mouse genotype signifies an initial defect that precipitates macrophage dysfunction. Of particular interest, the induction of remission in NZB/W lupus-prone mice led to a recovery of mitochondrial complex I gene expression and a correction of macrophage dysfunction in kidney-derived macrophages. Collectively, these observations imply that sustained, low-concentration IFN-γ impairs mitochondrial complex I function in macrophages, underscoring its role in the incipient stages of autoimmune disorders such as lupus nephritis. This work yields a novel understanding of the molecular dialogues that are fundamental to autoimmune development and points toward possible therapeutic entry points.
UR  - https://bprmcs.com/article/sustained-low-level-ifn-g-drives-mitochondrial-complex-i-dysfunction-and-macrophage-dysregulation-in-wksf2soa6fpriac
ER  -