The Unfolded Protein Response in Homeostasis and Modulation of Mammalian Immune Cells.
The endoplasmic reticulum (ER) plays important roles in eukaryotic protein folding and lipid biosynthesis. Several exogenous and endogenous cellular sources of stress can perturb ER homeostasis leading to the accumulation of unfolded proteins in the lumen. Unfolded protein accumulation triggers a signal-transduction cascade known as the unfolded protein response (UPR), an adaptive mechanism which aims to protect cells from protein aggregates and to restore ER functions. Further to this protective mechanism, in immune cells, UPR molecular effectors have been shown to participate in a wide range of biological processes such as cell differentiation, survival and immunoglobulin and cytokine production. Recent findings also highlight the involvement of the UPR machinery in the maturational program and antigen presentation capacities of dendritic cells. UPR is therefore a key element in immune system homeostasis with direct implications on both adaptive and innate immune responses. The present review summarizes the knowledge on the emerging roles of UPR signaling cascades in mammalian immune cells as well as the consequences of their dysregulation in relation to the pathogenesis of several diseases.
a Mass Spectrometry Centre, Department of Chemistry and QOPNA , University of Aveiro, Campus Universitário de Santiago , Aveiro , Portugal.
Ana Sofia
AS
Martins
a Mass Spectrometry Centre, Department of Chemistry and QOPNA , University of Aveiro, Campus Universitário de Santiago , Aveiro , Portugal.
Inês
I
Alves
a Mass Spectrometry Centre, Department of Chemistry and QOPNA , University of Aveiro, Campus Universitário de Santiago , Aveiro , Portugal.|b Institute for Research in Biomedicine - iBiMED, Health Sciences Program, Universidade de Aveiro , Portugal.
Luisa
L
Helguero
a Mass Spectrometry Centre, Department of Chemistry and QOPNA , University of Aveiro, Campus Universitário de Santiago , Aveiro , Portugal.
Maria Rosário
MR
Domingues
a Mass Spectrometry Centre, Department of Chemistry and QOPNA , University of Aveiro, Campus Universitário de Santiago , Aveiro , Portugal.|c Faculty of Pharmacy and Centre for Neuroscience and Cell Biology, University of Coimbra , Coimbra , Portugal.
Bruno Miguel
BM
Neves
D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D056890:Eukaryota / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D056811:Unfolded Protein Response / Q000502:physiology*
D016207:Cytokines; D007136:Immunoglobulins
ATF6; Endoplasmic reticulum stress; IRE1; PERK; Regulated Ire1-Dependent Decay; immune cells; unfolded protein response