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Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors’ Repertoire in the Recovery of Systemic Lupus Erythematosus

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Abstract

The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE’s pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as ‘‘smart” immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously.

Graphical Abstract

In Brief

The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes.

The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases.

Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis.

In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs.

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Data Availability

There is no data to share because the article is a review.

Abbreviations

Anti-dsDNA :

Anti-double stranded DNA

BAFF :

B activating-cell factor

Bcl-6 :

B-cell leukemia/lymphoma 6

BM :

Bone marrow

Breg :

Regulatory B cell

CCL2 :

C-C motif chemokine ligand 2

CCL18 :

C-C motif chemokine ligand 18

CCR6:

Chemokine receptor 6

CFU-Fs :

Fibroblast colony-forming units

CCR2 :

C-C chemokine receptor type 2

CXCR5 :

Chemokine Receptor 5

CXCR4 :

Chemokine Receptor 4

DC :

Dendritic Cell

FAS/FASL :

Fas and Fas ligand

GCs :

Germinal centers

HGF :

Hepatocyte growth factor

HLA :

Human leukocyte antigen

HLA-G5 :

Human leukocyte antigen-G5

ICAM-1 :

Intercellular adhesion molecule 1

ICOS :

Inducible T cell co-stimulator

IDO :

Indolamine 2, 3-dioxigenase

IFN-γ :

Interferon-gamma

IL :

Interleukin

M2 :

Alternative macrophage

MCP-1 :

Monocyte Chemotactic Protein-1

MHC :

Major histocompatibility complex

MSC :

Mesenchymal stem/stromal cell

MV :

Membrane vesicle

NO :

Nitric oxide

NF-κB :

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

PCs :

Plasma cells

PGE2 :

Prostaglandin E2

SLE :

Systemic lupus erythematosus

STAT3 :

Signal transducer and activator of transcription 3

Tfh :

T follicular helper

Tfr :

T follicular regulatory

TGF-β :

Transforming growth factor-beta

Th :

T helper cells

TNF-α :

Tumor necrosis alpha-factor

TRAF6/NF-κB :

TNF Receptor-associated factor 6

Tr1 :

Type 1 regulatory T cells

Treg :

T regulatory cell

TSG-6 :

Tumour necrosis factor-Stimulated gene 6

UV :

Ultraviolet

UC :

Umbilical cord

VCAM-1 :

Vascular cell adhesion molecule 1

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Authors and Affiliations

  1. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Akram Hoseinzadeh, Seyed-Alireza Esmaeili & Mahmoud Mahmoudi

  2. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Akram Hoseinzadeh, Jalil Tavakol Afshari, Seyed-Alireza Esmaeili & Mahmoud Mahmoudi

  3. Department of Rheumatology, Ghaem Hospital, Mashhad University of Medical Science, Mashhad, Iran

    Zahra Rezaieyazdi

  4. Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra Rezaieyazdi

  5. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Ali Mahmoudi

  6. Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Sahar Heydari

  7. Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Moradi

  8. Department of Immunology, Mashhad University of Medical Sciences, Azadi Square, Kalantari Blvd, Pardi’s campusMashhad, Iran

    Mahmoud Mahmoudi

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  1. Akram Hoseinzadeh
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Akram Hoseinzadeh has drafted the work.

Mahmoud Mahmoudi, Zahra Rezaieyazdi, Jalil Tavakol Afshari, Seyed-Alireza Esmaeili and Reza Moradi thoroughly reviewed it.

Ali Mahmoudi and Sahar Heydari have drawn the figures.

All authors read and approved the final manuscript.

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Correspondence to Mahmoud Mahmoudi.

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Hoseinzadeh, A., Rezaieyazdi, Z., Afshari, J.T. et al. Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors’ Repertoire in the Recovery of Systemic Lupus Erythematosus. Stem Cell Rev and Rep 19, 322–344 (2023). https://doi.org/10.1007/s12015-022-10452-7

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