Haematopoiesis

Essential and instructive roles of GATA factors in eosinophil development.Hirasawa, R. et al. J. Exp. Med. 195, 1379–1386 (2002)

Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo.Yu, C. et al. J. Exp. Med. 195, 1387–1395 (2002)

These papers show that the transcription factor GATA1 has a pivotal role in eosinophil development. Hirasawa et al. transduced human myeloid progenitors that were isolated from cord blood with GATA1 and found that they developed into eosinophils, even under culture conditions that favour the development of myeloid cells. Furthermore, they show that Gata1−/− mice lack eosinophil progenitors in the fetal liver. Yu et al. show that deletion of a positive regulatory element in the Gata1 promoter blocks eosinophil development. Together, these results indicate that GATA1 has an essential role in the specification of the eosinophil lineage.

Allergy

Human epithelial cells trigger dendritic-cell-mediated allergic inflammation by producing TSLP.Soumelis, V. et al. Nature Immunol. 3, 673–680 (2002)

Allergic inflammation is associated with the dysregulated production of T helper 2 (TH2) cytokines, such as IL-4, IL-5 and IL-13. The activation of dendritic cells (DCs) seems to be an important part of this process, but it is unknown what drives DCs to preferentially stimulate TH2-cell development. This study shows that human epithelial cells produce an IL-7-like cytokine, known as thymic stromal lymphopoietin (TSLP), which activates DCs and causes them to polarize naive CD4+ T cells for the production of TH2-associated cytokines. So, TSLP is a key trigger for DC-mediated allergic inflammation and might represent a new target for blocking inflammation, particularly in allergic diseases.

T-Cell Development

Dynamics of thymic–stromal-cell interactions visualized by two-photon microscopy.Bousso, P. et al. Science 296, 1876–1880 (2002)

Two-photon laser-scanning microscopy (TPLSM) allows immunologists to investigate the behaviour of immune cells in three dimensions in real-time analyses. Here, Bousso and colleagues use TPLSM to assess the interactions of thymocytes and stromal cells during positive selection in a reaggregated thymic organ culture system. Thymocyte–stromal-cell interactions were diverse, involving both dynamic and stable interactions, but the basis for this observed diversity is unclear. The next step will be to assess the signals that are received through the T-cell receptor of a single thymocyte during thymocyte development.