Immunometabolism - The Role of Branched-Chain Amino Acids


Yahsi B., GÜNAYDIN G.

FRONTIERS IN IMMUNOLOGY, vol.13, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 13
  • Publication Date: 2022
  • Doi Number: 10.3389/fimmu.2022.886822
  • Journal Name: FRONTIERS IN IMMUNOLOGY
  • Journal Indexes: Science Citation Index Expanded, Scopus, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: immunometabolism, T cells, regulatory T cells (Tregs), branched-chain amino acids (BCAAs), branched-chain keto acids (BCKAs), tumor microenvironment, isoleucine, REGULATORY T-CELLS, FATTY-ACIDS, METABOLIC CHECKPOINT, ACRODERMATITIS DYSMETABOLICA, GLUCOSE-METABOLISM, CD36 EXPRESSION, BINDING PARTNER, IN-VIVO, ACTIVATION, MTORC1

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.