Biomedical subjects

Ruran Mo

Publications and source records attributed to Ruran Mo.

4 recordsLinked to original sources

PubMed2006

Effect of aging on bone marrow-derived murine CD11c+CD4-CD8alpha- dendritic cell function.

Dendritic cells (DCs) are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and tumor surveillance functions of bone marrow-derived CD11c(+)CD4(-)CD8alpha(-) DCs of old and young C57BL/6 mice. Old immature bone marrow-derived CD4(-)CD8alpha(-) DCs (imDCs) were 4 times less effective than were young DCs in stimulating syngeneic CD4(+) T-cell proliferation. Old imDCs also have decreased DC-specific/intracellular adhesion molecule type 3-grabbing, nonintegrin (DC-SIGN) expression compared to young DCs. Interestingly, mice treated with the ovalbumin peptide-pulsed young DCs exhibited significantly greater tumor regression than with ovalbumin peptide-pulsed old DCs. Old terminally differentiated bone marrow-derived DCs (tDC) also have increased interleukin-10, but decreased interleukin-6 and tumor necrosis factor-alpha production. Taken together, these results have important implications in the clinical application of DC-based tumor immunotherapy in elderly persons.

Aging↗

PubMed2003

T cell chemokine receptor expression in aging.

Changes in chemokine receptor expression are important in determining T cell migration and the subsequent immune response. To better understand the contribution of the chemokine system in immune senescence we determined the effect of aging on CD4(+) T cell chemokine receptor function using microarray, RNase protection assays, Western blot, and in vitro chemokine transmigration assays. Freshly isolated CD4(+) cells from aged (20-22 mo) mice were found to express a higher level of CCR1, 2, 4, 5, 6, and 8 and CXCR2-5, and a lower level of CCR7 and 9 than those from young (3-4 mo) animals. Caloric restriction partially or completely restored the aging effects on CCR1, 7, and 8 and CXCR2, 4, and 5. The aging-associated differences in chemokine receptor expression cannot be adequately explained by the age-associated shift in the naive/memory or Th1/Th2 profile. CD4(+) cells from aged animals have increased chemotactic response to stromal cell-derived factor-1 and macrophage-inflammatory protein-1alpha, suggesting that the observed chemokine receptor changes have important functional consequences. We propose that the aging-associated changes in T cell chemokine receptor expression may contribute to the different clinical outcome in T cell chemokine receptor-dependent diseases in the elderly.

Aging↗

PubMed2003

Aging is associated with increased human T cell CC chemokine receptor gene expression.

Leukocyte chemokine receptors (CR) are central to the pathogenesis of many human diseases, including human immunodeficiency virus-1 (HIV-1) infection. Elderly individuals infected with the HIV-1 virus have a shorter disease-free interval and worse clinic outcome. However, the reasons for this are unclear. We recently reported increased CC chemokine receptor (CCR) expression in CD4+ T cells in aged mice, but it is not known if similar changes occur in humans. In addition, it is unclear if the observed differences are related to aged-related expansion in the memory T cell compartment. In this report, we examined the effects of aging on CCR gene expression in human peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and naive/memory T cells. Aging is found to be associated with increased CCR1-5 expression in PBMCs and CD4+ T cells. In addition, although the age-related increases in CCR expression occurred in both naive and memory T cells, the greatest changes were seen in the memory T cell subset. We propose that the observed aging-associated increase in T cell chemokine receptor expression may contribute to the worse clinical outcome of T cell chemokine receptor-dependent disease, such as HIV-1 infection, in the elderly.

Adolescent↗

PubMed2003

Aging is associated with increased T-cell chemokine expression in C57BL/6 mice.

To better understand the contribution of the chemokine system in immune senescence, we determined the aging effect on CD4+ and CD8+ T-cell chemokine expression by microarray screening and ribonuclease protection assays. Compared with young C57BL/6 mice, freshly isolated CD4+ cells from aged mice express increased level of interferon-gamma-inducible protein 10 (IP-10), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated upon activation, normal T-cell expressed and secreted (RANTES), and lymphotactin (Ltn). T-cell receptor (TCR)/coreceptor stimulation up-regulates MIP-1alpha, MIP-1beta, and Ltn, and down-regulates IP-10 and RANTES expression in CD4+ T cells. A similar increase in chemokine expression was demonstrated in the CD8+ T cell. Enzyme-linked immunosorbent assays confirmed increased T-cell chemokine protein production in old CD4+ and CD8+ T cells. Finally, supernatant of cultured T cells from old animals caused an enhanced leukocyte chemotaxis response compared with that from young animals, suggesting that the age-related difference in T-cell chemokine expression has an important functional consequence.

Aging↗