The Unfolded Protein Response: How Protein Folding Became a Restrictive Aspect for Innate Immunity and B Lymphocytes¹

Chaperone production is an essential step for proper folding of certain proteins. Accumulation of misfolded/unfolded proteins within the endoplasmic reticulum (ER) lumen triggers a signalling pathway named unfolded protein response (UPR). Upon activation, the UPR pathway augments transcription of ER chaperones increasing protein folding, decreases protein translation to ameliorate the ER overload, increases protein degradation, and activates the apoptotic programme if all previous measures fail. In this review, we will cover the chaperones involved in folding of proteins related to the immune response, followed by an overview of the UPR pathway. Lastly, we will discuss data from this last decade that demonstrate how the improper activation of the UPR pathway has been uncovered as a mechanism responsible for failure to mount a proper immune response, both innate and adaptive.