التفاصيل البيبلوغرافية
| العنوان: |
CD4+ T Cell-Derived NGAL Modifies the Outcome of Ischemic Acute Kidney Injury. |
| المؤلفون: |
Lee, Sul A.1, Noel, Sanjeev1, Kurzhagen, Johanna T.1, Sadasivam, Mohanraj2, Pierorazio, Phillip M.3, Arend, Lois J.2, Hamad, Abdel R.2, Rabb, Hamid1 hrabb1@jhmi.edu |
| المصدر: |
Journal of Immunology. Feb2020, Vol. 204 Issue 3, p586-595. 10p. |
| مصطلحات موضوعية: |
*ACUTE kidney failure, *T helper cells, *T cells, *TH2 cells, *TRANSFER functions |
| مستخلص: |
CD4+ T cells mediate the pathogenesis of ischemic and nephrotoxic acute kidney injury (AKI). However, the underlying mechanisms of CD4+ T cell-mediated pathogenesis are largely unknown. We therefore conducted unbiased RNA-sequencing to discover novel mechanistic pathways of kidney CD4+ T cells after ischemia compared with normal mouse kidney. Unexpectedly, the lipocalin-2 (Lcn2) gene, which encodes neutrophil gelatinase-associated lipocalin (NGAL) had the highest fold increase (〜60). The NGAL increase in CD4+ T cells during AKI was confirmed at the mRNA level with quantitative real-time PCR and at the protein level with ELISA. NGAL is a potential biomarker for the early detection of AKI and has multiple potential biological functions. However, the role of NGAL produced by CD4+ T cells is not known. We found that ischemic AKI in NGAL knockout (KO) mice had worse renal outcomes compared with wild-type (WT) mice. Adoptive transfer of NGAL-deficient CD4+ T cells from NGAL KO mice into CD4 KO or WT mice led to worse renal function than transfer of WT CD4+ T cells. In vitro-simulated ischemia/reperfusion showed that NGAL-deficient CD4+ T cells express higher levels of IFN-γ mRNA compared with WT CD4+ T cells. In vitro differentiation of naive CD4+ T cells to Th17, Th1, and Th2 cells led to significant increase in Lcn2 expression. Human kidney CD4+ T cell NGAL also increased significantly after ischemia. These results demonstrate an important role for CD4+ T cell NGAL as a mechanism by which CD4+ T cells mediate AKI and extend the importance of NGAL in AKI beyond diagnostics. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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