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2018 ; 9
(ä): 1465
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Regulation of the Immune Response by the Inflammatory Metabolic Microenvironment
in the Context of Allotransplantation
#MMPMID29988548
Degauque N
; Brosseau C
; Brouard S
Front Immunol
2018[]; 9
(ä): 1465
PMID29988548
show ga
Antigen challenge induced by allotransplantation results in the activation of T
and B cells, followed by their differentiation and proliferation to mount an
effective immune response. Metabolic fitness has been shown to be crucial for
supporting the major shift from quiescent to active immune cells and for tuning
the immune response. Metabolic reprogramming includes regulation of the balance
between glycolysis and mitochondrial respiration processes. Recent research has
shed new light on the functions served by the end products of metabolism such as
lactate, acetate, and ATP. At enhanced local concentrations, these metabolites
have complex effects in which they not only induce T and B cell responses, cell
mobility, and cytokine secretion but also favor the resolution of inflammation by
promoting regulatory functions. Such mechanisms are instrumental in the context
of the immune response in transplantation, not only to protect the graft and/or
eliminate cells targeting it but also to maintain cell homeostasis per se.
Metabolic adaptation thus plays an instrumental role on the outcome of the
cellular and humoral responses. This, of course, raises the possibility of drugs
that would interfere in these metabolic pathways to control the immune response
but also highlights the risk that some drugs may perturb this metabolism and cell
homeostasis and be deleterious for graft outcome. This review focuses on how
metabolic alterations of the local immune microenvironment regulate the immune
response and the impact of metabolic manipulation in allotransplantation.