TREML4 receptor regulates inflammation and innate immune cell death during polymicrobial sepsis
Journal Title
Nature Immunology
Publication Type
Journal epub ahead of print
Abstract
Sepsis is a biphasic disease characterized by an acute inflammatory response, followed by a prolonged immunosuppressive phase. Therapies aimed at controlling inflammation help to reduce the time patients with sepsis spend in intensive care units, but they do not lead to a reduction in overall mortality. Recently, the focus has been on addressing the immunosuppressive phase, often caused by apoptosis of immune cells. However, molecular triggers of these events are not yet known. Using whole-genome CRISPR screening in mice, we identified a triggering receptor expressed on myeloid cells (TREM) family receptor, TREML4, as a key regulator of inflammation and immune cell death in sepsis. Genetic ablation of Treml4 in mice demonstrated that TREML4 regulates calcium homeostasis, the inflammatory cytokine response, myeloperoxidase activation, the endoplasmic reticulum stress response and apoptotic cell death in innate immune cells, leading to an overall increase in survival rate, both during the acute and chronic phases of polymicrobial sepsis.
Publisher
NPG
WEHI Research Division(s)
Infectious Diseases And Immune Defence; Blood Cells And Blood Cancer
PubMed ID
33020659
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-10-17 02:40:36
Last Modified: 2020-11-03 10:16:26
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