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Author Spotlight: Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats
Published on: April 7, 2023
Functional Roles of Pattern Recognition Receptors That Recognize Virus Nucleic Acids in Human Adipose-Derived
Lili Yu1, Yongtao Xu2, Fangchao Wang1
1School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, China; Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang, Henan 453003, China.
Abstract:
Human adipose-derived mesenchymal stem cells (hAD-MSCs) are mesenchymal stem cells with the capability to modulate immune responses. Evidence showing that hAD-MSCs could mediate innate immune responses through pattern recognition receptors (PRRs) is increasing. However, the roles of PRRs in regulating the innate sensing of virus nucleic acids (RNA and DNA) in hAD-MSCs have not yet been investigated. This study focused on the abundant expression of PRRs, including Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I), which recognize viral RNA, and gamma-interferon inducible protein 16 (IFI16), which recognizes viral DNA in hAD-MSCs. Poly(I:C), a synthetic dsRNA analogy, activated TLR3 and RIG-I and induced the expression of type I interferons (IFN-α/β) and antivirus proteins, including IFN-stimulating gene 15, 2'5'-oligoadenylate synthetase, and Mx GTPase 1 in hAD-MSCs, which were attenuated by the knockdown of each TLR3 or RIG-I. Synthetic herpes simplex viral DNA (HSV60) activated IFI16 and induced the expression of IFN-α/β and antivirus proteins in hAD-MSCs, which were inhibited by the knockdown of IFI16. Both poly(I:C) and HSV60 induced the expression of IFN-α/β through the phosphorylation of IFN-regulatory factor 3. All these results indicated that PRRs recognizing virus nucleic acids were expressed and can mediate antivirus responses in hAD-MSCs.
Insights
Human adipose-derived mesenchymal stem cells express pattern recognition receptors (PRRs) that detect viral RNA and DNA. These PRRs activate antiviral responses, demonstrating their role in innate immunity.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Human adipose-derived mesenchymal stem cells (hAD-MSCs) modulate immune responses.
- Increasing evidence suggests hAD-MSCs mediate innate immunity via pattern recognition receptors (PRRs).
- The role of PRRs in sensing viral nucleic acids in hAD-MSCs remains unexplored.
Purpose of the Study:
- Investigate the expression and function of PRRs recognizing viral RNA and DNA in hAD-MSCs.
- Determine if these PRRs mediate antiviral responses in hAD-MSCs.
Main Methods:
- Assessed expression of Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I), and gamma-interferon inducible protein 16 (IFI16) in hAD-MSCs.
- Stimulated hAD-MSCs with poly(I:C) (synthetic viral RNA analog) and HSV60 (synthetic viral DNA analog).
- Utilized gene knockdown techniques for TLR3, RIG-I, and IFI16 to assess their roles in antiviral responses.
Main Results:
- hAD-MSCs express TLR3, RIG-I, and IFI16, which recognize viral RNA and DNA.
- Poly(I:C) and HSV60 activated TLR3/RIG-I and IFI16, respectively, inducing type I interferons (IFN-α/β) and antiviral proteins.
- Knockdown of TLR3, RIG-I, or IFI16 attenuated these antiviral responses.
- Both stimuli induced IFN-α/β via IFN-regulatory factor 3 phosphorylation.
Conclusions:
- PRRs recognizing viral nucleic acids are expressed in hAD-MSCs.
- These PRRs are functional and mediate antiviral responses in hAD-MSCs.
- hAD-MSCs possess an innate immune sensing capability against viral nucleic acids through PRRs.
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