# Function of circulating exosomes in sepsis-induced immunosuppression

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2021 · $197,938

## Abstract

Sepsis syndrome consists of a dysregulated host response to infection involving a complex interplay between 
proinflammatory and anti-inflammatory processes. Initially, sepsis is characterized by excessive cytokine 
release that shifts over time to a state of immune exhaustion characterized by T cell dysfunction and 
apoptosis. Although most sepsis-related deaths occur during this late hypoimmune state, there are currently 
no reliable biomarkers to stratify immune status of patients with sepsis to guide precision delivery of 
immunotherapeutic agents. Exosomes are membrane-bound nanovesicles containing miRNAs which are 
increasingly recognized as key regulators of host immune response. Leveraging recent advances in 
microfluidic detection of exosomes and associated cargo, the goal of this proposal is to accurately define key 
immune pathways disrupted in sepsis and to identify clinically useful biomarkers of immune status. Previous 
research has largely focused on the role of exosomes in mediating inflammation and endothelial dysfunction 
characteristic of septic shock; however, preliminary data from our laboratory challenge this paradigm and 
demonstrate that circulating exosomes also contribute to sepsis-induced immune suppression. Based on this 
premise, we hypothesize that sepsis results in immune dysfunction with corresponding changes in circulating 
concentrations of exosomal miRNA (exo-miRNA) that can be used as biomarkers of immune status. To test 
these hypotheses, we will execute the following Specific Aims: i) identify circulating exo-miRNA markers of 
sepsis; ii) evaluate the effect of plasma-derived exosomes from septic patients on immune function; and iii) 
develop a nanoengineered chip-based bioanalytic platform for the quantitation of exo-miRNA markers of 
sepsis. 
The candidate is a pharmacist-scientist with a proven commitment to translational science in infectious 
diseases and precision medicine. Additional skills in transcriptomics and bioanalytical assay development 
acquired through execution of this proposal will facilitate the candidate’s establishment of a research program 
devoted to optimizing the management of critically ill patients with life-threatening infectious diseases.

## Key facts

- **NIH application ID:** 10245054
- **Project number:** 5P20GM103638-10
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Nicholas S Britt
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,938
- **Award type:** 5
- **Project period:** 2020-06-27 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245054

## Citation

> US National Institutes of Health, RePORTER application 10245054, Function of circulating exosomes in sepsis-induced immunosuppression (5P20GM103638-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10245054. Licensed CC0.

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