IMMUNOMETABOLIC REGULATION OF TREGS: Multiple signaling networks, for instance, PI3K/Akt, mTOR-HIF-1α axis, and LKB1–AMPK pathways coordinate after immune cells are stimulated to mediate metabolic reprogramming. Here we focus on LKB1 signaling, in which LKB1 protein that restrains the activation and pro-inflammatory function of Teffs. LKB1 is a bioenergetic sensor that is expressed by the serine-threonine kinase 11 (STK11) gene and regulates cell polarity and function [79- 82]. It is an important upstream kinase that phosphorylates AMPKα (AMPK is heterotrimer having catalytic subunit (AMPKα) and regulatory subunit (AMPKβ and AMPKγ) ) that contributes to T cell differentiation and function and for maintaining functional fitness of Tregs in conditions of energy stress. [83]. Maclver et al. have reported that LKB1-AMPK signaling negatively regulates T cell effector function through the regulation of mTOR activity [84]. Of note, later studies have reported that the LKB1 signaling pathway promotes OXPHOS and FAO to maintain Treg survival and function. Furthermore, Nanhai et al. reported that LKB1 is crucial for maintaining cellular metabolism and energy homeostasis in Tregs and this metabolic phenotype is independent of AMPK and mTOR signaling pathways [85, 86]. To proof this, Nanhai et al. and others have deleted the LKB1 gene in Treg and catalytic subunit deletion of AMPK in Tregs. They found that LKB1 deletion resulted in loss of Tregs number and function and leads to impaired cellular metabolism in Tregs and uncontrolled immune activation. Contrary to this, the catalytic subunit deletion of AMPK in Tregs does not cause any abnormalities in the murine model. These findings are similar to those mice having mutations or deletion of FOXP3, where FOXP3 deletion resulted in loss of Tregs number. These studies further advocate the importance of LKB1 in Treg cell metabolism [80, 85-87].