Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance
An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8754 |
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| author | Luis F. Hernandez Luis R. Betancourt Ernesto S. Nakayasu Charles Ansong Gerardo A. Ceballos Daniel Paredes Midhat H. Abdulreda |
| author_facet | Luis F. Hernandez Luis R. Betancourt Ernesto S. Nakayasu Charles Ansong Gerardo A. Ceballos Daniel Paredes Midhat H. Abdulreda |
| author_sort | Luis F. Hernandez |
| collection | DOAJ |
| description | An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft’s immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft’s microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance. |
| first_indexed | 2024-03-10T08:44:41Z |
| format | Article |
| id | doaj.art-42d3424d7cbc4ef69146654c59b8bfbb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:41Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-42d3424d7cbc4ef69146654c59b8bfbb2023-11-22T08:00:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216875410.3390/ijms22168754Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus ToleranceLuis F. Hernandez0Luis R. Betancourt1Ernesto S. Nakayasu2Charles Ansong3Gerardo A. Ceballos4Daniel Paredes5Midhat H. Abdulreda6Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USAKnoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USABiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USABiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USAKnoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USAKnoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USADiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USAAn understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft’s immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft’s microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance.https://www.mdpi.com/1422-0067/22/16/8754anterior chamber of the eyeallogeneic islet transplantintraocular transplantimmune regulationLC-MS (liquid chromatography-mass spectrometry)MEKC-LIFD (micellar electrokinetic chromatography with laser induced fluorescence detection) |
| spellingShingle | Luis F. Hernandez Luis R. Betancourt Ernesto S. Nakayasu Charles Ansong Gerardo A. Ceballos Daniel Paredes Midhat H. Abdulreda Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance International Journal of Molecular Sciences anterior chamber of the eye allogeneic islet transplant intraocular transplant immune regulation LC-MS (liquid chromatography-mass spectrometry) MEKC-LIFD (micellar electrokinetic chromatography with laser induced fluorescence detection) |
| title | Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance |
| title_full | Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance |
| title_fullStr | Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance |
| title_full_unstemmed | Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance |
| title_short | Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance |
| title_sort | integrated metabolomics and proteomics analyses in the local milieu of islet allografts in rejection versus tolerance |
| topic | anterior chamber of the eye allogeneic islet transplant intraocular transplant immune regulation LC-MS (liquid chromatography-mass spectrometry) MEKC-LIFD (micellar electrokinetic chromatography with laser induced fluorescence detection) |
| url | https://www.mdpi.com/1422-0067/22/16/8754 |
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