Nkx2-3-A Slippery Slope From Development Through Inflammation Toward Hematopoietic Malignancies

The development of peripheral lymphoid tissues from the mesoderm is the result of a complex convergence combining lymphohematopoietic differentiation with the local specification of nonhematopoietic mesenchymal components. Although the various transcriptional regulators with fate-determining effects in diversifying the mobile leukocyte subsets have been thoroughly studied and identified, the tissue-specific determinants promoting the regional differentiation of resident mesenchyme are less understood. Of these factors, various members of the NK-class Nkx paralogues have emerged as key regulators for the organogenesis of spleen and mucosal lymphoid tissues, and recent data have also indicated their involvement in various pathological events, including gut inflammation and hematopoietic malignancies. Here, we summarize available data on the roles of Nkx2-3 in lymphoid tissue development and discuss its possible value as a developmental marker and disease-associated pathogenic trait.