preprints.org > biology and life sciences > immunology and microbiology > doi: 10.20944/preprints202402.0439.v2

Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 6 February 2024 / Approved: 7 February 2024 / Online: 7 February 2024 (11:38:55 CET)
Version 2 : Received: 7 February 2024 / Approved: 8 February 2024 / Online: 8 February 2024 (07:32:17 CET)

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

CD4; sepsis; Treg; metabolism

Biology and Life Sciences, Immunology and Microbiology

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