Kidney-Draining Lymph Node Fibrosis Following Unilateral Ureteral Obstruction.
Kidney-Draining Lymph Node Fibrosis Following Unilateral Ureteral Obstruction.
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DOI：
10.3389/fimmu.2021.768412
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kasinath V
中科院分区：
文献类型：
--
作者：
Li X;Zhao J;Naini SM;Sabiu G;Tullius SG;Shin SR;Bromberg JS;Fiorina P;Tsokos GC;Abdi R;Kasinath V
尽管在过去的几十年中，主要器官一直是器官纤维化领域中深入研究的主题，但由于其伴侣器官中免疫应答的持续激活而导致的淋巴结纤维化的存在在很大程度上仍然未知。以前，我们证明，激活免疫反应缺血再灌注损伤（IRI）和新月体肾小球肾炎（CGN）在肾脏与细胞外基质（ECM）的生产成纤维细胞网状细胞（FRC）的肾引流淋巴结（KLN）。在此，我们试图确定单侧输尿管梗阻（UUO）后KLN中的FRC是否会发生类似的纤维化。我们将6-8周龄的C57 BL/6 J小鼠进行UUO 2、7和14天。我们在每个时间点通过免疫荧光染色检查肾脏和KLN的微结构，并通过流式细胞术定量KLN中的免疫细胞群。未受UUO及其伴侣KLN影响的对侧肾脏用作对照。我们通过免疫荧光染色发现，FRC增加了ECM纤维的产生并重塑了UUO KLN的微结构，导致了反映肾脏变化的纤维化。我们还通过流式细胞术观察到，UUO KLN中CD 11b+抗原呈递细胞、CD 11 c+树突状细胞和活化的CD 4+和CD 8 + T细胞的数量显著高于引流未受影响对侧肾的KLN。TGFβ/TGFβR信号通路的表达上调，并与UUO KLN中的FRC共定位，提示纤维化背后的可能机制。在UUO后2天输尿管结扎的释放和损伤发作时FRC的消耗都阻止了肾脏和KLN中纤维化的进展。这些发现首次强调了UUO期间肾脏和KLN纤维化之间的关联，并为未来的研究奠定了基础，这些研究将更深入地研究FRC和KLN纤维化之间联系的机制。
Although the primary organ has been the subject of intense investigation in the field of organ fibrosis over the past several decades, the presence of lymph node fibrosis due to persistent activation of the immune response in its partner organ remains largely unknown. Previously, we demonstrated that activation of the immune response following ischemia-reperfusion injury (IRI) and crescentic glomerulonephritis (CGN) in the kidney was associated with extracellular matrix (ECM) production by fibroblastic reticular cells (FRCs) of the kidney-draining lymph node (KLN). Here, we sought to determine whether FRCs in the KLN become similarly fibrogenic following unilateral ureteral obstruction (UUO) of the kidney. We subjected 6–8-week-old C57BL/6J mice to UUO for 2, 7, and 14 days. We examined the microarchitecture of the kidney and KLN by immunofluorescence staining at each timepoint, and we quantified immune cell populations in the KLN by flow cytometry. The contralateral kidney unaffected by UUO and its partner KLN were used as controls. We found through immunofluorescence staining that FRCs increased production of ECM fibers and remodeled the microarchitecture of the UUO KLN, contributing to fibrosis that mirrored the changes in the kidney. We also observed by flow cytometry that the populations of CD11b+ antigen-presenting cells, CD11c+ dendritic cells, and activated CD4+ and CD8+ T cells were significantly higher in the UUO KLN than the KLN draining the unaffected contralateral kidney. Expression of the TGFβ/TGFβR signaling pathway was upregulated and colocalized with FRCs in the UUO KLNs, suggesting a possible mechanism behind the fibrosis. Both release of ureteral ligation at 2 days following UUO and depletion of FRCs at the time of injury onset halted the progression of fibrosis in both the kidney and the KLN. These findings for the first time highlight the association between fibrosis both in the kidney and the KLN during UUO, and they lay the groundwork for future studies that will investigate more deeply the mechanisms behind the connection between FRCs and KLN fibrosis.
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影响因子：
8.7
作者：
Estes JD
通讯作者：
Estes JD
影响因子：
13.6
作者：
Cochrane, AL;Kett, MM;Ricardo, SD
通讯作者：
Ricardo, SD
影响因子：
9.8
作者：
Knoblich K;Cruz Migoni S;Siew SM;Jinks E;Kaul B;Jeffery HC;Baker AT;Suliman M;Vrzalikova K;Mehenna H;Murray PG;Barone F;Oo YH;Newsome PN;Hirschfield G;Kelly D;Lee SP;Parekkadan B;Turley SJ;Fletcher AL
通讯作者：
Fletcher AL
影响因子：
8
作者：
Maarouf, Omar H.;Uehara, Mayuko;Abdi, Reza
通讯作者：
Abdi, Reza
DOI：
10.1152/ajprenal.00441.2003
发表时间：
2004-12-01
影响因子：
4.2
作者：
Ito, K;Chen, J;Felsen, D
通讯作者：
Felsen, D