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Regulation of CCL4 expression by miRNA125b in immune cells and its decline with aging

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIA

IMMUNO-4

Authors

  • N.L. Cheng
  • X. Chen
  • C. Nguyen
  • R. Wersto
  • N.P. Weng

Abstract

Aging is associated with the dys-regulation of chemokine expressions but the mechanisms underlying this alteration are not fully understood. MicroRNAs (miRNA) are key regulators for gene expression. Recently we identified high expression of miRNA125b and low expression of CC chemokine 4 (CCL4) in naïve CD8 T cells. Activation of naïve CD8 T cells by anti-CD3/28 resulted in increased CCL4 and decreased miRNA125b. Enhanced expression of miRNA125b in naïve CD8 T cells led to a reduced CCL4 in response to anti-CD3/28 stimulation. Mutagenesis study showed the miRNA125b “seed” sequence in 3’ UTR of CCL4 is required for its regulation. Extended analysis of other types of immune cells (CD4 and CD8 subsets, B cells and monocytes) showed a general inverse correlation between CCL4 mRNA and miRNA125b amount. Finally, monocytes expressed the highest amount of CCL4 among the examined immune cells and had a significant increase of CCL4 mRNA and decrease of miR-125b in old (≥ 70 yrs) compared to the young (≤ 42 yrs) adults. Together, these data demonstrated that miRNA125b is a negative regulator of CCL4 expression and suggested miRNA125b is partially responsible for the age-related increase of the inflammatory chemokine CCL4.

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