Fig. 9

Proposed mechanisms underlying differential action of miR-155 inhibition in young and aged mice. In young mice, inhibition of miR-155 leads to reduced formation of effector and memory CD8⁺ T-lymphocytes via downregulation of T-bet, whereas it has no measurable effect on microglia (A). In aged mice, reduced numbers of naïve CD8⁺ T-lymphocytes and elevated basal T-bet expression combine to obscure this effect of miR-155 (B). miR-155 inhibitor may cross the blood-brain barriers in aged mice and there inhibit infection-induced IFNγ-activation and M1-polarizaiton of microglia thereby limiting production of chemoattractants for recruiting leukocytes into the brain (C). Aging is accompanied by a shift of the immune response towards myelopoiesis, rendering these cells more susceptible to inhibition of miR-155 (D). Proposed mechanisms in C and D both result in reduced myeloid cell accumulation in the brain in mice treated with miR-155 inhibitor. Solid blue arrows represent the effect of miR-155 inhibitor in young mice, proposed effects of miR-155 in aged mice are represented by hatched blue arrows. Black arrows show the net effects of miR-155 inhibitor on leukocyte accumulation in the brain