Phagocytosis without inflammation

Thymocytes must pass a series of checkpoints on the road to becoming mature T cells. On page 603, Mandal et al. show that cells use Bcl2A1, a member of the Bcl2 family of survival proteins, to pass one critical checkpoint. The cell cannot make substitutes for this protein in a pinch, revealing that Bcl2A1 may be uniquely specialized for promoting survival without suppressing proliferation. To become mature T cells, thy-mocytes must express a functional T cell receptor (TCR). A requisite early step in fulfilling this goal is the expression of the pre-TCR—the ␤ chain of the mature TCR coupled with a pre– ␣ Pollen polarize dendritic cells How do pollen particles provoke allergic reactions? On page 627, Traidl-Hoffmann et al. put some of the blame on bioactive lipids that are released from pollen and cause dendritic cells (DCs) to initiate a T helper 2 (Th2)-biased, allergy-promoting immune response. This response may explain in part why increased car fumes are associated with greater prevalence of allergies. This group had discovered previously that pollen grains rapidly liberate eiconasoid-like substances, which are similar to prostaglandins and leukotrienes, when in an aqueous environment. These lipids bound to neutrophils and eosinophils (both involved in allergies and other immune reactions) and induced their activation, leading the group to propose that the release of these lipid mediators is an important event in allergic sensitization. What these data did not explain, however, was how the adaptive immune system becomes biased toward an allergy-inducing Th2 response. Traidl-Hoffmann et al. now show that soluble extracts from birch pollen and other common allergens inhibit the production of interleukin (IL)-12—the key cytokine involved in inhibiting Th2 responses—from activated DCs. These DCs could in turn bias naive T cells into becoming typical allergy-promoting Th2 cells. Biochemical analysis of these extracts allowed the authors to identify the culprit of the IL-12 inhibitory activity: a group of prostaglandin-like compounds called E1 phytoprostanes (PPE1). These results fit nicely with the known Th2-polarizing effect of human prostaglandin E2 (PGE2) on DCs. The signaling pathways are not identical, however, as PGE2, but not PPE1, also inhibits tumor necrosis factor (TNF) and IL-10. The function of these lipids in the plant is not completely clear, but they may be triggered in response to stress, as pollen DCs (blue) exposed to pollen lipids polarize T cells (yellow) toward a Th2 phenotype. exposed to air pollutants produce more of these compounds …