Year: 2016
Type: article
Abstract: Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor + (p75NTR + ) fibroblasts and homeostatic chemokine–producing fibroblasts inside TLTs, and retinoic acid–producing fibroblasts around TLTs. Deletion of CD4 + cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly.
Source: JCI Insight
Authors: Yuki Sato, Akiko Mii, Yoko Hamazaki, Harumi Fujita, Hirosuke Nakata, Kyoko Masuda, Shingo Nishiyama, Shinsuke Shibuya, Hironori Haga, Osamu Ogawa, Akira Shimizu, Shuh Narumiya, Tsuneyasu Kaisho, Makoto Arita, Masashi Yanagisawa, Masayuki Miyasaka, Kumar Sharma, Nagahiro Minato, Hiroshi Kawamoto, Motoko Yanagita
Institutions: Kyoto University, Kyoto University Hospital, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Wakayama Medical University, RIKEN Center for Integrative Medical Sciences, Howard Hughes Medical Institute, University of Tsukuba, International Institute for Integrative Sleep Medicine, University of Tsukuba, The University of Texas Southwestern Medical Center, University of Turku, The University of Osaka, University of California San Diego, VA San Diego Healthcare System
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: Clarification of transcriptional network that drives T cell lineage specification, Clarification of the intestinal immune regulatory mechanisms by dendritic cells, G385481923, G47037241, Analysis of human senescence-related T cells using cohort study, Elucidation of molecular mechanism of the robustness between T and B cell lineage, G6655660536, フォワードジェネティクスで同定した新規睡眠制御遺伝子による睡眠覚醒制御機構の解明, Molecular mechanism of the regulation of antigen-specific immune reaction
OpenAlex ID: W2504280359