Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease
Abstract
:1. Introduction
2. Allogeneic Haematopoietic Stem Cell Transplantation and the Graft-Versus-Tumour Effect
3. Acute Graft-versus-Host Disease
4. Purinergic Signalling
5. Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation
6. Purinergic Signalling in GVHD
7. P2X7 Receptor Signalling in GVHD
8. P2Y2 and P2Y12 Receptor Signalling in GVHD
9. Adenosine Receptor Signalling in GVHD
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviation
References
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Model | Graft | Host | Target | Drug Regime | Outcomes | Ref. |
---|---|---|---|---|---|---|
Allogeneic | 5 × 106 TCD a BM b cells + 1.6 × 106 (FVB/N) or 1 × 106 CD4+ /CD8+ (C57BL/6) (i.v. c) | BALB/c | eATP d | 4U Apyrase (hydrolysis catalyst) i.p. e days 0–2, 6–8 | ↑f Survival ↓g Apoptosis and inflammation in the gastrointestinal tract ↓ Serum IFN h-γ | [72] |
Allogeneic | 10 × 106 CD25 depleted T cells (C57BL/6) (injection route not disclosed) | BALB/c | eATP | 4U Apyrase (hydrolysis catalyst) i.p. days 0–4 | ↑ Survival | [110] |
Allogeneic | 5 × 106 BM cells and 2 × 105 CD4+/CD8+ splenic T cells (i.v.) | C57BL/6 | CD73 | 50 mg/kg APCP i (antagonist) i.p. days 0–6 | ↑ Mortality | [111] |
Allogeneic | 5 × 106 BALB/c splenocytes ± BM cells or splenocytes (i.v.) | C57BL/6 | CD73 | 20 mg/kg APCP (antagonist) i.v. twice weekly | ↑ Mortality ↑ Splenic CD4+ and CD8+ T cells ↑ Serum IFN-γ and ILj-6. | [112] |
Humanised | 10 × 106 hPBMCs k (i.p.) | NSG l | CD39 and CD73 | 50 mg/kg APCP (antagonist) i.p. days 0–6 | ↑ Weight loss ↑ Histological damage ↑ Serum human IL-2 | [113] |
Humanised | 20 × 106 CD25-depleted hPBMC + PBS, GMSCs m, human fibroblasts or nTregs n (i.v.) | NOD.Cg-Prkdcscid | CD39 | 100 μM POM-1 o (antagonist) was used to pretreat GMSCs | ↑ Mortality ↑ Histological damage ↑ Serum IL-4, IL-17, IFN-γ, IL-2 and TNFp-α. | [116] |
Model | Graft | Host | Target | Drug Regime (All Antagonists) | Outcomes | Ref. |
---|---|---|---|---|---|---|
Allogeneic | 5 × 106 TCD a BM b cells + 1.6 × 106 (FVB/N) or 1 × 106 CD4+ /CD8+ (C57BL/6) (i.v. c) | BALB/c | P2X7 | 10 µmol PPADS d i.p. e days 0–10 | ↑f Survival ↑ Tregsg, ↓ T cell expansion ↓h Serum IFNi-γ ↓ GVHD severity | [72] |
Allogeneic | 5 × 106 TCD BM cells + 1 × 106 CD4+ /CD8+ (C57BL/6) (i.v.) | BALB/c | P2X7 | 1 µmol KN62 i.p. days 0–10 | ↑ Survival | [72] |
Allogeneic | 10 × 106 CD25 depleted T cells (C57BL/6) (injection route not disclosed) | BALB/c | P2X7 | 80 mg/kg A-438079 i.p. day 0–4 | ↑ Survival | [110] |
Allogeneic | 10 × 106 TCD BM cells + 2.5 × 106 CD4+ T cells (C57BL/6) (injection route not disclosed) | BALB/c | P2X7 | 25 mg/kg Stavudine (d4T) i.p. twice daily from day −1 or 0 | ↑ Survival (when started from day −1) ↓ Serum IFN-γ, TNFj-α and ILk-6 ↓ Liver inflammation | [100] |
Allogeneic | 5 × 106 BM cells + 5 × 106 splenic cells (C57BL/6) (i.v.) | BALB/c | P2X7 | 50 mg/kg or 75mg/kg BBGl i.p. twice weekly for 4 weeks | ↓ Weight loss ↓ Liver inflammation ↓ CXCL8 and CCL2, Il1B and Il18 | [114] |
Humanised | 10 × 106 hPBMCsm (i.p.) | NSGn | P2X7 | 50 mg/kg BBG i.p. days 0, 2, 4, 6, 8, 10 | ↓ Serum IFN-γ ↓ Liver, skin and small intestine inflammation | [118] |
Humanised | 10 × 106 hPBMCs (i.p.) | NSG | P2X7 | 50 mg/kg BBG i.p. thrice weekly until endpoint | ↓ Liver inflammation | [119] |
Humanised | 10 × 106 hPBMCs (i.p.) | NSG | P2X7 | 50 mg/kg BBG i.p. days 0–10 | ↓ Clinical disease ↓ Liver and skin inflammation ↓ Serum IFN-γ ↑ Tregs and B cells | [117] |
Humanised | 10 × 106 hPBMCs (i.p.) | NSG | P2X7 | 300 mg/kg PPADS i.p. days 0–10 | ↑ Tregs | [117] |
Model | Graft | Host | Target | Drug Regime | Outcomes | Ref. |
---|---|---|---|---|---|---|
Allogeneic | 5 × 106 BMa cells and 2 × 105 CD4+/CD8+ splenic T cells (i.v.b) | C57BL/6 | Adenosine receptors | 10 mg/kg Caffeine (antagonist) i.p.c days 0–6 then 3–5 times a week | ↑d Mortality | [111] |
Allogeneic | 5 × 106 BALB/c splenocytes ± BM cells or splenocytes (i.v.) | C57BL/6 | A2A | 2 mg/kg SCH58261 (antagonist) i.p. days −2–12 | ↑ Mortality ↑ Splenic CD4+ and CD8+ T cells ↑ Serum IFNe-γ, TNFf-α and ILg-6 | [112] |
Allogeneic | 5 × 106 BALB/c splenocytes ± BM cells or splenocytes (i.v.) | C57BL/6 | A2B | 2 mg/kg MRS1754 (antagonist) i.p. days −2–12 | No differences | [112] |
Allogeneic | 10 × 106 C57BL/6 splenocytes ± 10 × 106 T cells (i.v.) | B6D2F1/J | A2A | 10 ng/kg ATL-146e (agonist) s.c. days 0–14 | ↑ Survival ↑ Serum IL-10 ↓h Splenic CD4+ and CD8+ T cells ↓ T cell infiltration into target organs ↓ Serum IFN-γ and IL-6 | [133] |
Humanised | 5 × 106 human Th1i cells and 3 × 106 human monocytes (i.p.) | NSGj | A2A | 1.5 mg/kg ZM241385 (antagonist) i.p. daily from disease onset until endpoint | ↑ Mortality ↑ Histological damage ↑ IFN-γ and TNF-α producing cells | [135] |
Humanised | 10 × 106 hPBMCsk (i.p.) | NSG | Adenosine receptors | 10 mg/kg Caffeine (antagonist) i.p. days 0–14 | No differences | [113] |
Humanised | 10 × 106 hPBMCs (i.p.) | NSG | A2A | 0.1 mg/kg CGS21680 (agonist) i.p. day −2–11 | ↑ Weight loss ↑ Serum human IL-6 ↓ Histological damage ↓ Serum human TNF-α | [136] |
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Cuthbertson, P.; Geraghty, N.J.; Adhikary, S.R.; Bird, K.M.; Fuller, S.J.; Watson, D.; Sluyter, R. Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease. Int. J. Mol. Sci. 2021, 22, 8343. https://doi.org/10.3390/ijms22158343
Cuthbertson P, Geraghty NJ, Adhikary SR, Bird KM, Fuller SJ, Watson D, Sluyter R. Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease. International Journal of Molecular Sciences. 2021; 22(15):8343. https://doi.org/10.3390/ijms22158343
Chicago/Turabian StyleCuthbertson, Peter, Nicholas J. Geraghty, Sam R. Adhikary, Katrina M. Bird, Stephen J. Fuller, Debbie Watson, and Ronald Sluyter. 2021. "Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease" International Journal of Molecular Sciences 22, no. 15: 8343. https://doi.org/10.3390/ijms22158343