Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction.
Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction.
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DOI:
10.1038/ki.2011.348
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发表时间:
2012-02
影响因子:
19.6
通讯作者:
中科院分区:
文献类型:
--
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Interleukin 17A-secreting T-helper 17 cells are pathogenic in inflammatory kidney diseases, but their intra-renal regulation is poorly understood. Mouse unilateral ureteral obstruction was examined to better define T-helper 17 cell dynamics during interstitial inflammation. Cell sub-types were analyzed by multi-color flow cytometry, by cell sorting and by their effects on in vitro-generated T-helper 17 cells. Interleukin 17A expression progressively increased in obstructed kidneys and was localised to CCR6+CCR4+/−CD4+ T-cells. Numbers of CCR6+CD4+ T-cells increased >10-fold by 72 hours, were enriched for interleukin 17A production and were highly proliferative by in vivo bromodeoxyuridine labelling. Secreted products from leukocytes of obstructed kidneys enhanced interleukin 17A production by in vitro-generated T-helper 17 cells. The T-helper 17-enhancing activity was identified as interleukin-1 produced by renal dendritic cells and monocytes. The in vivo validity of these findings was confirmed in mice lacking interleulin-1-receptor and in mice treated with a recombinant interleukin-1 receptor antagonist which exhibited reduced intra-renal T-helper 17 activity compared to control animals. Thus, the inflamed kidney accumulates CCR6+ T-helper 17 cells that undergo activation and proliferation. Production of interleukin 1 family cytokines by resident dendritic cells and infiltrating monocytes enhances intra-renal T-helper 17 activation in acute kidney injury.
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影响因子:
30.5
作者:
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者:
Sallusto, Federica
影响因子:
19.6
作者:
Dong, Xiangyang;Bachman, Lori A.;Miller, Melinda N.;Nath, Karl A.;Griffin, Matthew D.
通讯作者:
Griffin, Matthew D.
影响因子:
30.5
作者:
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者:
Littman, Dan R.
影响因子:
20.3
作者:
Kryczek, Ilona;Banerjee, Mousumi;Zou, Weiping
通讯作者:
Zou, Weiping
影响因子:
13.6
作者:
Gan, Poh-Yi;Steinmetz, Oliver M.;Holdsworth, Stephen R.
通讯作者:
Holdsworth, Stephen R.