Immunometabolism – The Role of Branched-Chain Amino Acids

Abstract

Immunometabolism has been the focus of extensive research over the last years, especially in terms of augmenting anti-tumor immune responses. Regulatory T cells (Tregs) are a subset of CD4+ T cells, which have been known for their immunosuppressive roles in various conditions including anti-tumor immune responses. Even though several studies aimed to target Tregs in the tumor microenvironment (TME), such approaches generally result in the inhibition of the Tregs non-specifically, which may cause immunopathologies such as autoimmunity. Therefore, specifically targeting the Tregs in the TME would be vital in terms of achieving a successful and specific treatment. Recently, an association between Tregs and isoleucine, which represents one type of branched-chain amino acids (BCAAs), has been demonstrated. The presence of isoleucine seems to affect majorly Tregs, rather than conventional T cells. Considering the fact that Tregs bear several distinct metabolic features in the TME, targeting their immunometabolic pathways may be a rational approach. In this Review, we provide a general overview on the potential distinct metabolic features of T cells, especially focusing on BCAAs in Tregs as well as in their subtypes.

GCs-beta and B-arrestins Regulate Nrf2 via NR4As Productive Pathway Mediated by B-adrenergic for Anti-inflammation and Adopting Myocardial and Immune Functions

“…Where GPCRs are essential for GCs-beta productions and consequently for Nrf2 synthesis. And In fact, increased growth of hormone-stimulated maize axes was positively correlated with an enhanced rpS6 phosphorylation [124]. So, in bref thé synthesis of S6K are necessary for modulating ATPase and GTPase production which necessary for OPA1 repairs followed by modulating GPCRs production which necessary for GCs-beta synthesis (upon synthase function) that GCs-beta are the basis for modulating Nrf2 synthesis and functions followed by SESN2 synthesis.…”

Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice

“…The pathways predominantly related to adaptive immunity were inversely correlated with BCAA degradation, while those predominantly related to innate immunity were positively correlated. Although lymphocytes do not remain in the heart for any length of time, BCAA are necessary for lymphocyte development and clonal expansion [42][43][44][45]. To assess any causal relationship between BCAA degradation and pathways in the small intestine we performed causal mediation analysis.…”

Can endocan serve as a molecular “hepatostat” in liver regeneration?

“…One such molecule is endocan (endothelial cell‑specific molecule‑1 [ESM‑1]), which is indeed a potential immunoinflammatory marker that is related with cardiovascular disease as well as tumor angiogenesis (Matano et al 2014 ; Chen et al 2021 ; Balta et al 2015 ). Endocan binds to lymphocyte function-associated antigen 1 (LFA-1) on human lymphocytes, monocytes, Jurkat cells; and inhibits its binding to intercellular adhesion molecule 1 (ICAM-1) and reducing LFA-1-mediated leukocyte activation as well as affecting the recruitment of circulating lymphocytes to inflammatory sites (Bechard et al 2001a ; Yahsi and Gunaydin 2022 ). Indeed, endocan was suggested to be a predictor of survival for patients with liver cirrhosis (Toshikuni et al 2015 ) as well as a biomarker for steatosis (Erman et al 2020 ; Klisic et al 2020 ), which is known to be associated with defective liver regeneration (Allaire and Gilgenkrantz 2018 ).…”