Thymopoiesis is Enhanced by Inhibition of gp130 Signaling in Young and Aged Mice (85.15)

Abstract

Normal aging is characterized by attenuation of cellular immune function and progressive decline in ability to respond to pathogens. Understanding mechanisms of immunosenescence with aging will enable development of targeted therapies for enhancing immune response. We previously reported that both human and mouse thymus aging is characterized by increased expression of IL-6 family cytokines. Further we demonstrated that these cytokines are directly suppressive and involute the thymus. IL-6 family cytokines activate the gp130 cell surface receptor on thymocytes, thus we hypothesized inhibition of gp130 receptor signaling will stimulate thymopoiesis in aged mice. To test this hypothesis we infused aged BALB/c mice (20 mo) or young mice (2 mo) with neutralizing gp130 Ab and monitored thymus function over 8 weeks. Inhibition of gp130 signaling significantly elevated thymus weight and TCR gene rearrangement in the aged thymus. In young mice we also observed with gp130 inhibition significant increases in thymus weight, cellularity, TCR gene rearrangement, and naïve export to the periphery. Overall, these data demonstrate release of thymosuppressive cytokine signaling stimulates thymopoiesis by both young and aged thymus tissue. Furthermore, gp130 signaling is an important thymoregulatory pathway to explore in the pursuit of human T cell immune reconstitution therapies. Supported by NIH HL67314, AG025150.