Reining in Responses

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Science  09 Aug 2013:
Vol. 341, Issue 6146, pp. 593
DOI: 10.1126/science.341.6146.593-d

In response to infections, dendritic cells acquire microbial antigens and present them to T cells, and this leads to the induction of adaptive immunity. Although the dendritic–T cell interaction is essential to turn on the innate immune response, this interaction must also be turned off (or at least turned down) so as to avoid an overly aggressive response, as is observed in allergy and chronic inflammatory diseases. Carrera Silva et al. describe one such off switch that operates in mice and humans. Upon engagement of antigen-laden dendritic cells, T cells increased the expression of protein S (Pros1), which is a ligand for TAM-family receptor tyrosine kinases, which are expressed by dendritic cells. Conditional deletion of Pros1 in T cells in mice demonstrated that Pros1 was essential to keep dendritic cell activation in check, and the dendritic cells in these mice expressed more cytokines and activation markers. The loss of Pros1 on T cells in mice also led to worsened colitis and enhanced T cell–mediated immunity in vivo. Pros1 expressed on T cells did signal through TAM receptors; the deletion of TAM receptors in dendritic cells phenocopied mice with a T cell–specific deletion of Pros1. A similar expression and function of Pros1 were seen in human T cells, suggesting that this negative regulatory mechanism is evolutionarily conserved.

Immunity 39, 160 (2013).

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