Chemokines

The role of CCL21 in recruitment of T-precursors to fetal thymi. Liu, C. et al. Blood 105, 31–39 (2005).

In this study, Liu et al. developed a new in vitro time-lapse visualization technique to investigate the mechanisms that regulate the recruitment of T-cell precursors to the fetal thymus. Initial analysis showed that a proportion of fetal liver cells, blood cells or DN1 thymocytes were actively attracted towards an alymphoid fetal thymic lobe and that these cells were T-cell precursors. Recruitment of the T-cell precursors was mediated by MHC-class-II-expressing thymic epithelial cells and was abrogated in the presence of an inhibitor of G-protein-coupled receptors. Subsequently, the chemokines CCL21 and CCL25 were shown, using several assays, to contribute significantly to the active recruitment of T-cell precursors to the fetal thymus. Further studies are required to determine the molecular mechanism by which these chemokines mediate this effect.

Innate immunity

Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor. Choe, K. -M. et al. Proc. Natl Acad. Sci. USA 102 1122–1126 (2005).

Drosophila melanogaster peptidoglycan-recognition protein LC (PGRP-LC) is a transmembrane protein that is required for antibacterial responses mediated by a signalling pathway that involves the death-domain protein IMD and the nuclear factor-κB-family member Relish. Because the cytoplasmic domain of PGRP-LC has no sequence homology to characterized proteins, it is not known how it activates intracellular signalling. Using truncated PGRP-LC mutants, the authors show that its cytoplasmic domain binds IMD and is crucial for the induction of downstream signalling. The cytoplasmic domain also promotes dimerization of PGRP-LC, which might be required for its activation and might increase the diversity of ligand recognition through heterodimerization with other PGRP-LC isoforms.

Dendritic cells

Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo. Kerksiek, K. M. et al. Blood 105, 742–749 (2005).

Previous in vitro studies have indicated that the RHO guanosine triphosphatase RAC1 is important for endocytosis and cross-presentation by dendritic cells (DCs). In this paper, the authors confirm these results in vivo. Because knocking out RAC1 function in mice is embryonic lethal, they generated transgenic mice that express a DC-specific dominant-negative form of RAC1. Transgenic mice showed defective CD8+ DC development and function, and although DC migration was unaffected, apoptotic-cell uptake and cross-presentation by CD8+ DCs was severely impaired. This reduced their ability to induce bacteria-specific T-cell responses, indicating an important role for RAC1 in CD8+ DC function in vivo.