T-cell signalling
A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation. Zhao, H. et al. J. Immunol. 174, 5288–5297 (2005)
When screening for molecules involved in T-cell activation downstream of T-cell receptor (TCR) ligation, Zhao et al. identified a cDNA encoding a carboxy (C)-terminally truncated form of an uncharacterized protein. As the full-length protein contained a RING (really interesting new gene)-finger domain at its amino terminus, the authors named the new molecule T-cell RING protein identified in activation screen 1 (TRAC1). Consistent with the presence of a RING-finger domain, TRAC1 had RING-finger-dependent E3 ubiquitin ligase activity. And endogenous TRAC1 functioned as a positive regulator of T-cell activation downstream of TCR ligation. By contrast, C-terminally truncated TRAC1 inhibited TCR-induced CD69 upregulation, indicating the importance of this domain for TRAC1 function.
Mast cells
Möller et al. investigated the molecular mechanisms by which stem-cell factor (SCF) promotes mast-cell survival. SCF induced phosphorylation of forkhead box O3A (FOXO3A) in bone-marrow-derived cultured mast cells (BMCMCs). Consistent with phosphorylation of FOXO3A resulting in its inactivation, SCF prevented expression of BIM (B-cell lymphoma 2 (BCL-2)-interacting mediator of cell death), a pro-apoptotic member of the BCL-2 family, the gene encoding which is a FOXO3A target. Further analysis indicated that SCF also induced phosphorylation of BIM, which has been linked with proteasome-mediated degradation. Together with the observation that Bim−/− BMCMCs showed increased viability following SCF withdrawal, these data characterize a mechanism for SCF-regulated mast-cell survival.
Allergy
The relationship between airway smooth muscle (ASM) growth and T-cell-mediated airway inflammation in asthma is poorly understood. So, to study this, antigen-specific CD4+ T cells were isolated from sensitized rats and transfected with green fluorescent protein before being transferred to naive recipients. After repeated antigen challenge, the transferred cells induced a marked inflammatory response with CD4+ T-cell infiltration in the airways. The infiltrating T cells co-localized with ASM cells and led to increased ASM growth. This T-cell–myocyte crosstalk was also evident in vitro: ASM cells proliferated on direct contact with activated CD4+ T cells, and reciprocally, activation-induced T-cell death was inhibited in a contact-dependent manner. These data implicate CD4+ T cells as promoters of pathology in asthma.
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In Brief. Nat Rev Immunol 5, 433 (2005). https://doi.org/10.1038/nri1643
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DOI: https://doi.org/10.1038/nri1643