Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance

Autor: L. Betancourt, Charles Ansong, Daniel Paredes, Midhat H. Abdulreda, Gerardo Ceballos, Ernesto S. Nakayasu, Luis F. Hernandez
Rok vydání: 2021
Předmět:
Graft Rejection
Male
Islets of Langerhans Transplantation
intraocular transplant
Proteomics
Immune tolerance
Mice
anterior chamber of the eye
Insulin-Secreting Cells
M2 macrophages
Biology (General)
LC-MS (liquid chromatography-mass spectrometry)
M1 macrophages
Spectroscopy
tolerance
geography.geographical_feature_category
General Medicine
Allografts
Islet
metabolomics
Warburg effect
Tregs (T regulatory cells)
Computer Science Applications
Chemistry
Type 1 diabetes
medicine.anatomical_structure
Transplantation Tolerance
rejection
Teff (T effector cells)
QH301-705.5
Article
Catalysis
Inorganic Chemistry
proteomics
Immune system
Metabolomics
medicine
Metabolome
Animals
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
geography
pancreatic islets
MEKC-LIFD (micellar electrokinetic chromatography with laser induced fluorescence detection)
business.industry
Pancreatic islets
immune regulation
Organic Chemistry
allogeneic islet transplant
Immunology
T1D
business
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 8754, p 8754 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 16
ISSN: 1422-0067
DOI: 10.3390/ijms22168754
Popis: 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.
Databáze: OpenAIRE
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