Research Papers:

Expansion of myeloid-derived suppressor cells with arginase activity lasts longer in aged than in young mice after CpG-ODN plus IFA treatment

María F. Harman, Romina P. Ranocchia, Carolina V. Gorlino, María F. Sánchez Vallecillo, Sofía D. Castell, María I. Crespo, Belkys A. Maletto, Gabriel Morón and María C. Pistoresi-Palencia _

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Oncotarget. 2015; 6:13448-13461. https://doi.org/10.18632/oncotarget.3626

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María F. Harman1, Romina P. Ranocchia1, Carolina V. Gorlino1, María F. Sánchez Vallecillo1, Sofía D. Castell1, María I. Crespo1, Belkys A. Maletto1, Gabriel Morón1, María C. Pistoresi-Palencia1

1Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina

Correspondence to:

María C. Pistoresi-Palencia, e-mail: cpistore@fcq.unc.edu.ar

María Florencia Harman, e-mail: mharman@fcq.unc.edu.ar

Keywords: aging, myeloid-derived suppressor cells, arginase, CpG-ODN, immunomodulation

Received: February 18, 2015     Accepted: March 15, 2015     Published: April 13, 2015


As we age, the homeostatic function of many systems in the body, such as the immune function declines, which in turn contributes to augment susceptibility to disease. Here we describe that challenging aged mice with synthetic oligodeoxynucleotides containing unmethylated cytosine guanine motifs (CpG-ODN) emulsified in incomplete Freund's adjuvant (IFA), (CpG-ODN+IFA) an inflammatory stimulus, led to the expansion of CD11b+Gr1+ myeloid cells with augmented expression of CD124 and CD31. These myeloid cells lasted longer in the spleen of aged mice than in their younger counterparts after CpG-ODN+IFA treatment and were capable of suppressing T cell proliferative response by arginase induction. Myeloid cells from aged CpG-ODN+IFA-treated mice presented increased arginase-1 expression and enzyme activity. In addition, we found a different requirement of cytokines for arginase induction according to mice age. In myeloid cells from young treated mice, arginase-1 expression and activity is induced by the presence of each IL-4 or IL-6 in their extracellular medium, unlike myeloid cells from aged treated mice which need the presence of both IL-4 and IL-6 together for arginase induction and suppressor function.

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