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Toll-Like Receptor 3

A Multifunctional Regulator of Mesenchymal Stem Cells

  • Living reference work entry
  • First Online:
Handbook of Stem Cell Therapy

Abstract

Mesenchymal stem/progenitor cells (MSCs) are prospective cellular candidates for numerous regenerative and immunotherapeutic purposes. Their immunomodulatory potential and multilineage abilities allow them to be deployed for the treatment of various conditions. Nevertheless, depending on the local microenvironment, different biological tasks of MSCs can be adjusted. Toll-like receptors (TLRs) represent important bridges regulating the cross talk between MSCs and their microenvironment affecting diverse biological features of the cells. Toll-like receptor 3 (TLR3), a member of TLR family, recognizes double-stranded RNA (dsRNA) produced by DNA viruses and positive-strand RNA viruses. Its expression has been displayed by MSCs of various sources. Upon ligand identification inside the endosomes, TLR3 oligomerizes and recruits the Toll-interleukin-1 receptor domain-containing adaptor molecule-1 (TICAM-1), which triggers the production of NF-κB, β-catenin, IRF3, and AP-1, leading to the secretion of interferons and other immunomodulatory cytokines and results in pathogen clearance, as well as the recruitment of adaptive immune responses. It may also be involved in the cell-fate determination and cell cycle regulation in different developmental stages of the MSCs. Moreover, it has been shown to improve the therapeutic potential of MSCs by the promotion of multifunctional trophic factors. Priming of MSCs’ TLR3 within potential treatment procedures may serve as an additional step enhancing the required biological functions of the cells in different stages of the disease.

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Abbreviations

AD:

Adipose tissue

AKT:

Protein kinase B

AP-1:

Activator protein 1

AT-MSCs:

Adipose tissue mesenchymal stem cells

BM-MSCs:

Bone marrow mesenchymal stem cells

C/EPB:

Ccaat/Enhancer-binding protein

CFUS:

Colony forming units

COX-2:

Cyclooxygenase-2

DF-MSCs:

Dental follicle mesenchymal stem cells

DP-MSCs:

Dental pulp mesenchymal stem cells

DSRNA:

Double-stranded ribonucleic acid

G-MSCs:

Gingival mesenchymal stem cells

GSK3Β:

Glycogen synthase kinase 3 Β

HGF:

Hepatocyte growth factor

HO:

Hemoxygenase

IDO:

Indoleamine-2,3-dioxygenase

IKK:

Iκb kinase

INF1:

Interferone type 1

IRAK1:

Interleukin-1 receptor-associated kinase 1

IRF3/7:

Interferon regulatory factor 3/7

IΚB:

Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor

JNK:

C-Jun N-terminal kinase

LPS:

Lipopolysaccharides

MAPK:

Mitogen-activated protein kinase

MIF:

Macrophage migration inhibitory factor

MIRNA:

Micro-RNA

MKK:

Mitogen-activated protein kinase kinase

MSC:

Mesenchymal stem cell

MTOR:

Mechanistic target of rapamycin

MYD88:

Myeloid differentiation primary response 88

NF-ΚB:

Nuclear factor kappa-light-chain-enhancer of activated B cell

NK-CELLS:

Natural killer cells

NM-MSCs:

Nasal mucosa MSCs

NO:

Nitric oxide

P38:

P38 mitogen-activated protein kinases

PAMPS:

Pathogen-associated molecular patterns

PD-L1:

Programmed death ligand-1

PGE2:

Prostaglandin E2

PI3K:

Phosphatidylinositol 3-kinase

PIP2:

Phosphatidylinositol 4,5-bisphosphate

PMN:

Neutrophils

POLY(I:C) HMW:

High molecular weight polyinosinic-polycytidylic acid

PRR:

Pattern recognition receptor

PT:

Placental tissue

RIP1:

Receptor-interacting serine/Threonine-protein kinase 1

SCAP:

Stem cells from the apical papilla

S-SCR:

Cellular sarcoma molecule

SSRNA:

Single-stranded RNA

TAB1/2:

Tgf-beta-activated kinase ½

TAK1:

Mitogen-activated protein kinase kinase kinase 7

TBK1:

Tank-binding kinase 1

TH1:

Cd4+ T helper 1

TIR:

Toll-interleukin receptor domain

TLR:

Toll-like receptor

T-MSCS:

Mesenchymal stromal cells from human tonsils

TRAF:

Tnf-receptor-associated factor

TRIF:

Tir-domain-containing adapter-inducing interferon-Β

UCB:

Umbilical cord blood

UCB-MSCS:

Umbilical cord blood mesenchymal stem cells

WJ:

Wharton jelly

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  1. Mohamed Mekhemar and Johannes Tölle contributed equally with all other contributors.

Authors and Affiliations

  1. Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrecht’s University, Kiel, Germany

    Mohamed Mekhemar, Johannes Tölle, Christof Dörfer & Karim M. Fawzy El-Sayed

  2. Oral Medicine and Periodontology Department, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt

    Karim M. Fawzy El-Sayed

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  1. Mohamed Mekhemar
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  2. Johannes Tölle
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  4. Karim M. Fawzy El-Sayed
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Editors and Affiliations

  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia

    Khawaja H. Haider

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  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia

    Khawaja H. Haider

  2. University of Modena and Reggio Emilia, Modena, Italy

    Beatrice Aramini

  3. Interamerican Open University, Buenos Aires, Argentina

    Elio A. Prieto Gonzalez

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Mekhemar, M., Tölle, J., Dörfer, C., Fawzy El-Sayed, K.M. (2022). Toll-Like Receptor 3. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_25-1

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