| First Author | Lee SA | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 3 | Pages | 586-595 |
| PubMed ID | 31889023 | Mgi Jnum | J:284034 |
| Mgi Id | MGI:6388983 | Doi | 10.4049/jimmunol.1900677 |
| Citation | Lee SA, et al. (2020) CD4(+) T Cell-Derived NGAL Modifies the Outcome of Ischemic Acute Kidney Injury. J Immunol 204(3):586-595 |
| abstractText | 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 ( approximately 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-gamma 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. |
