Integrated metabolomics and proteomics analyses in the local milieu of islet allografts in rejection versus tolerance

Luis F. Hernandez, Luis R. Betancourt, Ernesto S. Nakayasu, Charles Ansong, Gerardo A. Ceballos, Daniel Paredes, Midhat H. Abdulreda

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number8754
JournalInternational journal of molecular sciences
Volume22
Issue number16
DOIs
StatePublished - Aug 2 2021

Keywords

  • Allogeneic islet transplant
  • Anterior chamber of the eye
  • Immune regulation
  • Intraocular transplant
  • LC-MS (liquid chromatography-mass spectrometry)
  • M1 macrophages
  • M2 macrophages
  • MEKC-LIFD (micellar electrokinetic chromatography with laser induced fluorescence detection)
  • Metabolomics
  • Pancreatic islets
  • Proteomics
  • Rejection
  • T1D
  • Teff (T effector cells)
  • Tolerance
  • Tregs (T regulatory cells)
  • Type 1 diabetes
  • Warburg effect

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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