Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance.
Int J Mol Sci
; 22(16)2021 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-34445459
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.
Palavras-chave
LC-MS (liquid chromatography-mass spectrometry); M1 macrophages; M2 macrophages; MEKC-LIFD (micellar electrokinetic chromatography with laser induced fluorescence detection); T1D; Teff (T effector cells); Tregs (T regulatory cells); Type 1 diabetes; Warburg effect; allogeneic islet transplant; anterior chamber of the eye; immune regulation; intraocular transplant; metabolomics; pancreatic islets; proteomics; rejection; tolerance
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante das Ilhotas Pancreáticas
/
Tolerância ao Transplante
/
Proteômica
/
Células Secretoras de Insulina
/
Metabolômica
/
Rejeição de Enxerto
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos