Novel mitophagy inducer alleviates lupus nephritis by reducing myeloid cell activation and autoantigen presentation.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), but its mechanism of onset remains unclear. Since impaired mitophagy has been implicated in multiple organs in SLE, we hypothesized that mitophagy dysfunction is critical in the development of LN and that pharmacologically targeting mitophagy would ameliorate this disease. Therefore, lupus-prone MRL/MpJ-Faslpr (MRL/lpr) and NZBWF1/J mice were treated with a novel mitophagy inducer, UMI-77, during their onset of LN. This treatment effectively mitigated kidney inflammation and damage as assessed by histology and flow cytometry. Furthermore, dendritic cell (DC)-T-cell coculture assay indicated that UMI-77 treatment attenuated DC function that would drive T-cell proliferation but did not directly influence the potent T-cell proliferation in lupus mice. UMI-77 also restored mitochondrial function and attenuated proinflammatory phenotypes in lupus DCs. Adoptive transfer of DCs from MRL/lpr mice augmented serum anti-dsDNA IgG, urine protein and T-cell infiltration of the kidney in MRL/MpJ mice, which could be prevented by either treating lupus donors in vivo or lupus DCs directly with UMI-77. UMI-77 also restored mitochondrial function in myeloid cells from patients with LN in vitro as evidenced by increased ATP levels. Thus, enhancing mitophagy in SLE restrains autoimmunity and limits kidney inflammation for LN development. Hence, our findings suggest targeting mitophagy as a tangible pathway to treat LN.

Particle-attached microorganism oxidation of ammonia in a hypereutrophic urban river.

To elucidate the importance and mechanisms of particle-attached microorganisms on ammonia oxidation, we conducted a controlled simulation experiment with samples collected from the Shunao River, an ammonia-rich hypereutrophic urban river in eastern China. The effects of particle concentration, ammonia concentration, organic carbon source and concentration, dissolved oxygen concentration, and pH were investigated on ammonia transformation rate (ammonia removal rate and NO2 - + NO3 - accumulation rate) and abundance of particle-attached ammonia-oxidizing bacteria (AOB) and archaea (AOA). All these factors significantly influenced ammonia transformation rates. Our results provided direct evidence that microorganisms attached on riverine suspended particles were associated with ammonia oxidation. Sequencing revealed that the AOA genus Nitrososphaera, and the AOB genus Nitrosomonas were the most dominant in particle-attached ammonia-oxidizing microbial communities. Further analysis showed that AOB communities had higher species richness and diversity compared with AOA communities. Additionally, AOB amoA genes were ~10-100 times more abundant than AOA amoA genes, and AOB abundance was more strongly correlated with ammonia transformation rates than AOA abundance in most experiments, indicating that particle-attached AOB were more important than AOA in the hypereutrophic urban river. This study adds to our knowledge of particle-attached microorganism oxidation of ammonia.