Inflammation

Essential role for proteinase-activated receptor-2 in arthritis. Ferrell, W. R. et al. J. Clin. Invest. 111, 35–41 (2003)

The G-protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated previously as a mediator of acute inflammation. Here, Ferrell et al. used an adjuvant monoarthritis model to investigate the role of PAR2 in chronic inflammation. Par2−/− mice were generated and used in these studies. The severity of chronic arthritis was reduced by a factor of more than four in the Par2−/− mice compared with wild-type mice. In addition, PAR2 agonists had potent pro-inflammatory effects, resulting in prolonged joint swelling and vasodilation. So, PAR2 has an essential role in mediating chronic inflammation, and it might be an important therapeutic target for the management of chronic inflammatory diseases.

Thymocyte Development

Thymopoiesis independent of common lymphoid progenitors. Allman, D. et al. Nature Immunol. 4, 168–174 2003

Thymocytes develop from blood-borne haematopoietic progenitors that seed the thymus, but the source of these early thymic progenitors (ETPs) is unknown. Common lymphoid progenitors (CLPs) in adult bone marrow, which can develop into B or T cells, were seen as a likely suspect. However, as this study shows, ETPs and CLPs differ with respect to their responsiveness to interleukin-7 and the kinetics with which they generate B and T cells. Also, Ikaros−/− mice, which have normal T-cell development, but are blocked for B-cell development, have normal levels of ETPs although CLPs are undetectable. Therefore, the authors conclude that ETPs develop from an early progenitor population that is distinct from CLPs.

Myeloid Development

Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation Hock, H. et al. Immunity 18, 109–120 (2003)

Previous studies have shown that the transcription factors PU.1, C/EBPα and C/EBPε are essential for neutrophil differentiation. Here, Hock et al. show that the nuclear zinc-finger transcriptional repressor Gfi1 is also intrinsically required for neutrophil development. Gfi1−/− mice survive to ∼11 weeks of age, and they are highly susceptible to abscess formation by Gram-positive bacteria. Mature neutrophils were shown to be absent from the blood of these gene-targeted mice, and immature neutrophils were lacking in the bone marrow. Instead, morphologically arrested, atypical Gr1+Mac1+ myeloid cells with characteristics of both neutrophils and macrophages (respiratory burst and phagocytosis) were present. Re-expression of Gfi1 in Gfi1−/− granulocyte/monocyte progenitors rescued normal neutrophil differentiation and blocked development of the atypical myeloid cells.