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A sphingosine derivative recruits regulatory T cells to the kidney by nuclear translocation of NFKB and up‐regulation of CCL5
Author(s) -
Ly Elina,
Yong Kim-Chong,
Lien Yeong-Hau H,
Lai Li-Wen
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.615.3
Subject(s) - ccl5 , chromosomal translocation , chemistry , il 2 receptor , kidney , inflammation , microbiology and biotechnology , medicine , cancer research , immunology , t cell , biology , biochemistry , gene , immune system
A sphingosine‐derivative (SD) has been identified which ameliorates renal ischemic reperfusion injury and recruits regulatory (Treg) and effector T cells to the inflamed tissues. The underlying mechanisms of this protection were investigated. Depleting the Treg by anti‐CD25 antibodies abolished this protection, suggesting that Treg recruited by SD play a key role. Using real time qRT‐PCR, we found that SD rapidly increased CCL5 mRNA in mouse kidney (3–4 folds increase at 1 h), which is known to direct T cell migration. To examine if this up‐regulation is mediated by activation of NFKB, a transcription factor known to regulate CCL5, we measured NFKB protein in renal proximal tubular cells before and after SD treatment by immunofluorescence stain and ArrayScan® VTI HCS reader. SD increased NFKB nucleus/cytosol ratio up to 80%. This nuclear translocation is dose‐dependent (1–20 uM) and was observed within 15 min, reached a plateau at 30 min and remained stable for 2h. In conclusion, our findings are consistent with the hypothesis that SD triggers the cascade of NFKB activation, leading to NFKB nuclear translocation and up‐regulation of CCL5 in renal tubule cells to recruit T cells into the kidney. Studies are ongoing to further pinpoint SD's role in upstream signaling pathway of NFKB activation and to develop a novel Treg‐based therapy for inflammatory diseases. Funding: NIH RO1DK82718, ABRC, DCI.