A new RIDDle in DC-mediated cross-presentation

Abstract

Hyperactivity of a branch of the unfolded protein response in CD8α⁺ dendritic cells degrades endoplasmic reticulum–associated mRNAs, which leads to a defect in the cross-presentation of dead cell–derived antigens.

Figure 1

Possible mechanisms by which RIDD compromises the cross-presentation of dead cell–derived antigens in CD8α⁺ DCs. Deletion of XBP-1 (XBP-1^Δ) in CD8α⁺ DCs leads to hyperactivation of IRE-1α, which leads to the cleavage of multiple mRNAs by endonucleases (RIDD). The main consequence observed by Osorio et al. is defective cross-presentation of dead cell–derived antigens. In theory, one or more mRNAs encoding proteins involved in the various stages of antigen cross-presentation (bold purple font) could be relevant targets of RIDD. Osorio et al. have identified several mRNA substrates of RIDD that could be involved, such as Lamp1, Tapbp and Ergic3, but the roles of their products remain to be demonstrated. Moreover, the specificity for dead cell–derived antigens rather than soluble or endogenous antigens raises the possibility that one or more molecules involved in the uptake and/or processing of dead cells may be the relevant targets of RIDD. TCR, T cell antigen receptor; MHCI, MHC class I.