Functional Roles of Pattern Recognition Receptors That Recognize Virus Nucleic Acids in Human Adipose-Derived Mesenchymal Stem Cells.

Lili Yu,Guoyan Liu,Fangchao Wang,Yongtao Xu,Can Yang,Xiangfeng Song

doi:10.1155/2016/9872138

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.

Highlights

Mesenchymal stem cells (MSCs) are multipotent adult stem cells capable of differentiation to many cell types, such as adipocytes, osteoblasts, chondrocytes, tendinocytes, myocytes [1]
The results showed that pattern recognition receptors (PRRs) that recognized viral RNA, including Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I), as well as DNA recognition receptor interferon inducible protein 16 (IFI16), were highly expressed at a comparable level in hAD-MSCs, compared with ThP1 cells, a monocytic human cell line used as a positive control (Figure 1(a))
Indirect immunofluorescence staining showed that the localization of RIG-I and TLR3 was expressed in cytoplasm, and IFI16 was expressed in both the cytoplasm and nucleus (Figure 1(c))

Summary

Introduction

Mesenchymal stem cells (MSCs) are multipotent adult stem cells capable of differentiation to many cell types, such as adipocytes, osteoblasts, chondrocytes, tendinocytes, myocytes [1]. MSCs can reportedly be isolated from different organs and functions as a source of cells for replacement and regeneration [2]. Apart from modulating differentiation potential [4], hAD-MSCs can modulate immune response [6]. Evidence showing that hAD-MSCs possess immunosuppressive properties is increasing [7, 8]. They could inhibit the activation, proliferation, and function of immune cells, including

Methods

Results

Conclusion