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 | |
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 | / | |
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 | / | |
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] |