The canonical Wnt/β-catenin signaling pathway is involved in the development of innate T cells in the thymus under infectious/inflammatory systemic conditions.

CONSTANZA SAVID FRONTERA; BAEZ NATALIA; MOTRAN CRISTINA; VOLPINI XIMENA; MARIA CECILIA RODRIGUEZ GALAN

Mar del Plata

Congreso; LXVI Reunión Científica Anual de la Sociedad Argentina de Inmunología (SAI); 2018

Sociedad Argentina de Inmunología y Sociedad Argentina (SAI) de Investigación Clinica (SAIC)

Our previous work demonstrated that during the acute stage of Th1 inflammatory or infectious processes, SP CD8 thymocytes alter their differentiation from ?conventional? to ?innate? lineage due to thymic production of IL-4 and IL15. Innate CD8+ cells express a particular phenotype (CD44hi CD122hi EOMEShi), produce high levels of IFNgama and have high cytotoxic activity. We demonstrated that the innate phenotype gives rise as early as the double positive (DP) stage in the thymus. The aim of our work was to determinate the molecular mechanisms that are involved in this differentiation.The canonical Wnt/β-catenin signaling pathway participates both in the differentiation of CD8+ T cells and the generation of functional CD8+ memory T cell. To investigate whether this pathway is involved in the generation of innate CD8+ cells, CD45.1+ control thymocytes were co-cultured with CD45.2+ thymocytes from control or T. cruzi-infected mice (the source of thymic IL-4/IL-15) in the presence or absence of the β-catenin activator lithium chloride (LiCl) or the inhibitor of β-catenin signaling, iCRT. Activation of β-catenin induced up-regulation of CD44, CD122 and EOMES in the CD45.1+ SP CD8 control thymocytes (p