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Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
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Human red blood cells express the RNA sensor TLR7
L K Metthew Lam1, Emily Oatman2, Kaitlyn A Eckart1
1Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Scientific Reports
|July 9, 2024
Summary
Human red blood cells (RBCs) express toll-like receptor 7 (TLR7), an RNA sensor. This finding reveals a new function for RBCs in binding and potentially clearing exogenous RNA from the body.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- Red blood cells (RBCs) are known to express toll-like receptor 9 (TLR9), which binds DNA.
- The expression and function of other nucleic acid-binding toll-like receptors (TLRs) on human RBCs remain largely unexplored.
Purpose of the Study:
- To investigate whether human RBCs express other nucleic acid-binding TLRs, specifically the RNA sensor TLR7.
- To determine the localization and interactions of TLR7 within RBCs.
- To explore the role of RBCs in binding exogenous RNA.
Main Methods:
- Immunofluorescence and Western blot analysis to detect TLR7 expression on RBCs.
- Co-immunoprecipitation to assess the association between TLR7 and the RBC membrane protein Band 3.
- In vitro binding assays using synthetic single-stranded RNA (ssRNA) and viral RNA.
- Analysis of TLR7-Band 3 interactions in RBCs from patients with SARS-CoV2-associated sepsis.
Main Results:
- Human RBCs express the RNA sensor TLR7 on their cell membrane.
- TLR7 is associated with the RBC membrane protein Band 3.
- RBCs demonstrate the ability to bind synthetic ssRNA and RNA derived from ssRNA viruses.
- Increased TLR7-Band 3 interactions were observed in RBCs from patients with SARS-CoV2-associated sepsis compared to healthy controls.
Conclusions:
- Human RBCs express TLR7, indicating a novel role in sensing and binding exogenous RNA.
- The association of TLR7 with Band 3 suggests a specific mechanism for RNA interaction within RBCs.
- RBCs may function as a previously unrecognized "sink" for exogenous RNA, contributing to immune responses and expanding their known non-gas exchanging functions.

