WSX1 exposed to positive and negative influences

A recent report in The Journal of Immunology indicates that expression of the ligand-specific component of the interleukin-27 (IL-27) receptor, WSX1, is differentially regulated after activation of distinct lymphoid-cell populations — WSX1 expression is increased after T-cell activation but decreased after natural killer (NK)-cell or natural killer T (NKT)-cell activation.

Initial reports indicated that the level of mRNA encoding WSX1 was decreased after activation of naive CD4⁺ T cells and that WSX1-deficient mice were more susceptible to infection with intracellular pathogens. Therefore, it was proposed that IL-27 is an important factor for the activation of naive CD4⁺ T cells to mediate type 1 immunity. However, subsequent studies showed that IL-27 was an inhibitor of effector T cells: WSX1-deficient mice infected with Toxoplasma gondii generated an appropriate immune response but succumbed to an inflammatory disease.

So Villarino et al. set out to study the level of expression of WSX1 on the lymphoid-cell populations that are known to have a role in controlling infection with T. gondii. A significantly lower proportion of NK cells and NKT cells (which are activated during the acute phase of infection) expressed high levels of WSX1 in mice infected with T. gondii than in uninfected animals. Furthermore, those cells still expressing high levels of WSX1 retained an unactivated phenotype, indicating that downregulation of WSX1 correlates with cellular activation. By contrast, the proportion of CD4⁺ and CD8⁺ T cells (which are required for resistance to infection with T. gondii) expressing high levels of WSX1 was increased after infection. Furthermore, the WSX1^hiCD4⁺ T cells had an effector phenotype, indicating that WSX1 upregulation correlates with T-cell activation.

Consistent with a role for T-cell activation as a regulator of WSX1 expression, T-cell-receptor crosslinking on CD4⁺ T cells in vitro resulted in increased cell-surface expression of WSX1, although this increase was only transient. Interestingly, upregulation of WSX1 required that the cells entered the cell cycle, but continued cell division was associated with the decrease in WSX1 expression levels. Additional signals that negatively regulate WSX1 expression levels were shown to come from IL-2.

This study indicates that activation of distinct lymphoid cells results in differential regulation of WSX1 expression levels and that both positive and negative signals can regulate this process, both in distinct cell types and within a responding population of cells.