Arg1+ monocytes in sepsis functionally attenuate systemic immune-mediated hyperinflammation: a novel therapeutic strategy to combat patient mortality

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B636
Abstract ID: 7481

Presenting Author:
Jacob E Williams , Undergraduate Researcher at Univ. of California, Berkeley, Broad Inst. of MIT and Harvard

Abstract:

Sepsis is a life-threatening disease characterized by systemic, immune-mediated hyperinflammation capable of inducing organ failure independent of persistent infection. As a result, sepsis is a pervasive barrier to patient survival that contributes to 1-in-5 deaths worldwide, highlighting the need for strategies to attenuate hyperinflammation to improve patient outcomes. Here, we investigate the origin and function of a unique monocyte population, termed Monocyte State 1 (MS1) cells, noted for their emergence during chronic inflammation in humans. Our methods involved a multiplexed, temporal approach to sc-RNA-seq, leveraging oligonucleotide hashtagging for precise localization and time-specific immune cell profiling after induction of sepsis via cecal ligation and puncture in mice. Results revealed the emergence of Arginase-1 positive (Arg1+) cells in mouse tissues as early as 12h post-induction of sepsis which appear to originate from MS1 cells that become pathologically activated in bone marrow and rapidly migrate to peripheral tissues. Validation of their kinetics via flow cytometry markers shows that IL-1R2+ MS1 cells precede the emergence of Arg1+ MS1 cells in the blood and tissues of septic mice. Collectively, our results advance understanding of MS1 cell biology in sepsis and indicate a novel ontological route for Arg1+ MS1 cells that may be exploited for the development of molecular or cell-based therapeutics in the treatment of patients with sepsis.