Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

The interplay between the CD4-1ineage transcription factor ThPok and the CD8-iineage transcription factor, runt-related transcription factor 3 （Runx3）, in T-cell development has been extensively documented. However, little is known about the roles of these transcription factors in invariant natural killer T （iNKT） cell development. CDld-restricted iNKT cells are committed to the CD4＋CD8- and CD4-CD8- sublineages, which respond to antigen stimulation with rapid and potent release of T helper （Th） 1 and Th2 cytokines. However, previous reports have demonstrated a new population of CD8~ NKT cells in ThPok-deficient mice. In the current study, we sought to determine whether Runx3 was involved in the re-expression of CD8 and function of iNKT cells in the absence of ThPok. We used mice lacking Runx3, ThPok or both and verified that Runx3 was partially responsible for the appearance of CD8^＋ iNKT cells in ThPok knockout mice. Additionally, Runx3 participated in the immune response mediated by iNKT cells in a model of α-galactosylceramide-induced acute hepatitis. These results indicate that Runx3 is crucial for the phenotypic and functional changes observed in ThPok-deficient iNKT cells.

Loss of microRNAs in thymus perturbs invariant NKT cell development and function

microRNAs(miRNAs)are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level.Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development,including autoimmune diseases.Invariant natural killer T(iNKT)cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses.Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells.In the present study,to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development,we generated a mouse model with the Dicer deletion in the thymus.Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs.miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon a-galactosylceramide(a-GalCer)stimulation.Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.