ARGINASE INDUCTION IN MYELOID CELLS FROM CPG-ODN+IFA-TREATED MICE

MARÍA FLORENCIA HARMAN; SOFÍA DAIANA CASTELL; CAROLINA V. GORLINO; MARÍA INÉS CRESPO; MARÍA FERNANDA SÁNCHEZ VALLECILLO; ROMINA P. RANOCCHIA; BELKYS ANGELICA MALETTO; GABRIEL MORÓN; MARÍA CRISTINA PISTORESI

Mar del Plata

Congreso; LXII Reunión Científica de la Sociedad Argentina de Inmunología; 2014

Previously we showed that challenging young and aged mice with CpG-ODN+IFA leads to the expansion of CD11b+Gr1+ myeloid cells. These cells suppressed T-cell proliferative response by an arginase dependent mechanism, thus, the addition of an arginase inhibitor restored T-cell proliferation. We also showed in these myeloid cells an increased arginase-1 expression and activity. In order to evaluate the environmental factors involved in arginase induction we measured the cytokines present in the culture medium. IL-4 and IL-6 levels were augmented in cultures of myeloid cells from young and aged CpG-ODN+IFA-treated mice with stimulated T-cells from young mice. In line with this, we observed increased phosphorylation of Stat6 and Stat3 (transcription factors activated by IL-4 and IL-6 respectively) in these myeloid cells. The neutralization of IL-4 or IL-6 in the culture medium led to an almost complete reduction of arginase-1 expression and activity in myeloid cells from aged CpG-ODN+IFA-treated mice, which also occurred when both neutralizing antibodies were added together (p˂0.01). Although in myeloid cells from young CpG-ODN+IFA-treated mice the neutralization of either IL-4 or IL-6 reduced Arginase-1 expression and activity, only the absence of both cytokines reduced it completely. In resume, myeloid cells from CpG-ODN+IFA mice are activated in response to their local environmental signals. IL-4 and IL-6 from the extracellular medium are involved in arginase induction. The presence of either IL-4 or IL-6 is sufficient for arginase induction in myeloid cells from young treated mice whereas in the case of aged animals, both cytokines are required.