Deep profiling of lupus nephritis kidneys reveals dynamic changes in myeloid cells associated with disease progression.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hoover Paul J, Eisenhaure Thomas M, Hodgin Jeffrey, Apruzzese William, Mears Joseph, Peters Michael, Jones Tony, Shah Sujal I, Kamal Haniya, Leavitt Rollin, Jackson Shaun W, Danaher Patrick, Rao Deepak A, Xiao Qian, Gurajala Siddarth, Ai Junting, Fava Andrea, Berthier Celine C, Horisberger Alice, Barnas Jennifer L, Izmirly Peter M, Belmont H Michael, Clancy Robert, Furie Richard, Aranow Cynthia, Guthridge Joel M, Dall'Era Maria, Wofsy David, Kamen Diane L, Kalunian Kenneth C, McMahon Maureen A, Grossman Jennifer, Payan-Schober Fernanda, Hildeman David A, Woodle E Steve, Putterman Chaim, Kretzler Matthias, Clark Marcus R, Raychaudhuri Soumya, James Judith A, Anolik Jennifer H, Petri Michelle A, Buyon Jill P, Accelerating Medicines Partnership (AMP) RA/SLE Network, Diamond Betty, Davidson Anne, Hacohen Nir, Arazi Arnon
Аннотация
METHODS: We used single-cell RNA-sequencing (scRNA-seq) data of dissociated kidney samples from 156 patients with LN and 30 healthy individuals. We applied spatial transcriptomics (ST), utilising a gene panel designed to capture all myeloid subsets identified in the scRNA-seq data, to profile kidney samples acquired from 6 patients with LN and 2 controls.
RESULTS: We generated a catalogue of the myeloid subsets found in LN kidneys. Our analyses indicated that an increase in irreversible tissue damage, as measured by the National Institutes of Health chronicity index (CI), is associated with a gradual switch of the local immune response from one dominated by monocytes and macrophages to one featuring expanded CD4 T, GZMK+ CD8 T, B, and dendritic cells, with a parallel decrease in the interferon response. In proliferative/mixed LN only, the degree of active inflammation correlates with the expansion of disease-specific macrophage (DMac) subsets, which later contract as the CI increases. Trajectory analysis of the scRNA-seq data suggested that DMacs arise from both infiltrating monocytes and tissue-resident macrophages; this was supported by the ST data, as well as cell cultures. DMacs are implied to interact with parietal epithelial cells, promoting the development of glomerulosclerosis.
CONCLUSIONS: We suggest a detailed picture of the changes in the kidney immune mechanisms in LN as this disease progresses.