At the crossway of ER‐stress and proinflammatory responses

• Published in: The FEBS journal 2019-01, Vol.286 (2), p.297-310
• Main Authors: Reverendo, Marisa, Mendes, Andreia, Argüello, Rafael J., Gatti, Evelina, Pierre, Philippe
• Format: Article
• Language: English
• Subjects: Animals; Cascades; Cell survival; Cytokines; Damage detection; Dendritic cells; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - pathology; Endoplasmic Reticulum Stress; Hazards; Humans; Immune system; Immunity; Immunity, Innate - immunology; Immunology; inflammation; Inflammation - physiopathology; Inflammatory diseases; Innate immunity; Life Sciences; Metabolism; Pathogenesis; Protein folding; Proteins; Rescue operations; Signal Transduction; Signaling; Unfolded Protein Response
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.14391

Immune cells detect specific microbes or damage to tissue integrity in order to initiate efficient immune responses. Abnormal accumulation of proteins in the endoplasmic reticulum (ER) can be seen as a sign of cellular malfunction and stress that triggers a collection of conserved emergency rescue programs. These different signaling cascades, which favor ER proteostasis and promote cell survival, are collectively known as the unfolded protein response (UPR). In recent years, a synergy between the UPR and inflammatory cytokine production has been unraveled, with different branches of the UPR entering in a cross‐talk with specialized microbe sensing pathways, which turns on or amplify inflammatory cytokines production. Complementary to this synergetic activity, UPR induction alone, can itself be seen as a danger signal, and triggers directly or indirectly inflammation in different cellular and pathological models, this independently of the presence of pathogens. Here, we discuss recent advances on the nature of these cross‐talks and how innate immunity, metabolism dysregulation, and ER‐signaling pathways intersect in specialized immune cells, such as dendritic cells (DCs), and contribute to the pathogenesis of inflammatory diseases. A synergy between the unfolded protein response (UPR) and inflammatory cytokines production has been unraveled. This biochemical cross‐talk between microbe sensing pathways and protein homeostasis regulation ensures that immune and inflammatory responses are commensurate to the threat levels posed by infection. UPR induction is itself a danger signal, that triggers directly or indirectly inflammation in several metabolic diseases.