Table 2 The ways MSCs on the adaptive immune responses during LI.

From: Mesenchymal stem cells for lung diseases: focus on immunomodulatory action

Lung diseases

Animal model

Intervention (MSCs/EVs)

Regulation of immune cells

Outcomes

Mechanism

References

IPF

Aspirated bleomycin in C57BL/6 mice

BMSCs

Increased numbers of Tregs

Reduced fibrosis and inflammation;

Up-regulated circulating TGF-β1

/

[130]

IPF

Instilled intratracheally with bleomycin in C57BL/6 mice

hAMSCs

Increased Treg cell marker Foxp3; Reduced pulmonary B-cell recruitment, retention, and maturation

Decreased alveolar obliteration;

Decreased extracellular matrix proteins and α‐SMA

/

[21]

PF

Injected intratracheally with bleomycin in Rag2−/−γc−/− mice

BMSCs

Inhibited the proliferation of anti-CD3–stimulated human CD45 lymphocytes as well as CD4 and CD8 T cells

Suppressed proinflammatory cytokines such as IFN-γ, TNF-α, and IP-10

PD-1/PD-L1 Pathway

[20]

PF

Administered paraquat to Sprague-Dawley rats

hAMSCs

Reduced CD3 + T lymphocyte accumulation

Decreased collagen deposition;

Improved histopathological changes;

Decreased levels of lactic acid and inflammatory cytokines in the plasma

/

[68]

ALI

Injected intratracheally with LPS in C57BL/6 mice

MSCs

Decreased immunoglobulin-related gene expression in lung B cells

Decreased chemokines CCL3, CCL4 and IL-6, IFN-γ

/

[75]

ALI

Injected intratracheally with LPS in Balb/C mice

hUCMSCs

Increased

CD4 + CD25+ Foxp3+Treg cells;

Decreased IFN-r-producing Th1 cells

Reduced inflammatory cytokines;

Increased anti- inflammatory factor IL-10

/

[131]

ALI

Injected intratracheally with LPS in C57BL/6 mice

LRMSCs

Increased the percentage of Tregs and reduced the percentage of Th17 cells

Reduced inflammatory cells and decreased the inflammatory cytokines IL-1β, IL-6, and TNF-α;

Increased the expression of KGF-2 and SPC;

Decreased deposition of interstitial collagen;

Increased IL-10 and reduced IL-17, IL-22

/

[63]

ALI

Injected intratracheally with LPS in C57BL/6 mice

BMSCs

Increased the percentage of Treg cells and decreased the percentage of Th17 cells

Decreased MPO activity;

Attenuated IL-6 and IL-17

/

[64]

ALI

Injected intratracheally with LPS in C57BL/6 mice

MSCs

Down-regulated Ly6C+CD8+T cells

Reduced inflammatory factors

/

[67]

Asthma

Injected intraperitoneally with OVA in BALB/c mice

BMSCs

Increased the frequencies of CD4 + CD25+Treg cells

Reduced the number of inflammatory cells and airway hyperresponsivensess;

Increased IL-10 and IL-12

Regulated Jagged-1 signalling

[132, 133]

Asthma

Injected intraperitoneally with OVA in BALB/c mice

AMSCs/ hUCMSCs

Enhanced Tregs expansion

Reduced airway hyperresponsivensess, lung inflammation, and mucus production;

Decreased IgE and IgG1;

Down-regulated Th2 cytokines and up-regulated Th1 cytokines

/

[134, 135]

Asthma

Injected intraperitoneally with OVA in Sprague-Dawley rats

hPMSCs

Increased the frequencies of Treg cells;

Reduced the frequencies of Th17 positive cells

Reduced the number of inflammatory cells;

Increased IL-10 and reduced IL-17

/

[65]

Asthma

Injected intraperitoneally with OVA in BALB/c mice

IFN -γ-and ‘ IFN -γ + TNF -α‘ treated AMSCs

Improved Treg cell and Th9 related parameters ratio and shift T cell response toward Treg cells

Attenuated lung inflammation;

Reduced IL-9 and increased IL-35

/

[136]

Asthma

Inoculate with Aspergillus fumigatus hyphal extract in C57Bl/6 mice

BMSCs/ BMSC-CM/BMSC-EVs

/

Alleviated airway hyper-responsiveness and inflammation;

Decreased of Th2 and Th17 soluble mediators

/

[137, 138]

Asthma

Instillated intranasally

with house dust mite in BALB/c mice

BMSCs

Reduced the number of activated and antigen-acquiring CD11c + CD11b+ dendritic cells

Alleviated airway hyper-responsiveness and inflammation;

Decreased the expression of the pro-Th2 cytokine IL-25

/

[139]

Asthma

Injected intraperitoneally with OVA in BALB/c mice

hUCMSCs

/

Alleviated lung inflammation;

Reduced Th2 cytokine IL-5

/

[140]

Asthma

Injected intraperitoneally with OVA in Wistar rats

BMSC-CM

/

Modulated the T-bet, GATA-3, IL-4 and IFN-γ

/

[141]

Asthma

Instillated intranasally

with Alternaria alternata and house dust mite /diesel exhaust particle in BALB/c mice

hUCMSCs

/

Down-regulated the IL-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells

/

[142]

COPD

Sprague-Dawley rats were exposed to tar and nicotine

BMSCs

Reduced the frequency of Th17 and Th1 cells, increased the frequency of Tregs

Mitigated anti-elastin responses and inflammatory infiltrates;

Modulated the imbalance of cytokine and chemokines

/

[143]

COPD

Sprague-Dawley rats were exposed to nicotine

BMSCs

inhibited the proliferation of nicotine‑exposed T cells

/

Down-regulated iNOS expression in BMSCs and enhanced STAT5 phosphorylation in T cells

[144]

LCHS

Used the blast wave of a percussive nail gun in Sprague-Dawley rats; Withdrawn blood then re-infused in Sprague-Dawley rats

MSCs

Expanded the Treg cell population

Decreased total lung injury score

/

[145]

RILI

Radiated with 20 Gy 60Co γ-ray in C57BL/c mice

Decorin-modified UCMSCs

Down-regulated Treg cells

Attenuated histopathological injury;

Inhibited inflammatory cytokines and Chemokines;

Alleviated lung fibrosis

/

[146]

IPS

Radiated with 8 Gy 60Co γ-ray in BALB/c mice

BMSCs

Inhibited T cell activation and proliferation

Alleviated lung pathological damage

Regulated CCR2-CCL2 axis

[147]

  1. IPF Idiopathic pulmonary fibrosis, ALI Acute lung injury, LCHS Lung contusion followed by hemorrhagic shock, PF Pulmonary Fibrosis, COPD Chronic obstructive pulmonary disease, IPS Idiopathic pneumonia syndrome, hAMSCs Human amniotic membrane mesenchymal stromal cells, CM Conditioned medium, hUCMSCs Human umbilical cord mesenchymal stem cells, BMSCs Bone marrow-derived mesenchymal stem cells, AMSCs Mesenchymal stem cells derived from adipose tissue, hPMSCs human placenta mesenchymal stem cells, LRMSCs Lung-resident- mesenchymal stem cells, EVs Extracellular vesicles, Treg cell T regulatory cell, IL-6 Interleukin-6, IFN-γ Interferon-γ, KGF Keratinocyte growth factor, SPC surfactant protein C, LPS Lipopolysaccharide