Chemical individuality in T cells: A Garrodian view of immunometabolism

Abstract

Metabolically quiescent T cells circulate throughout the body in search of antigen.Following engagement of their cognate receptors, T cells undergo metabolic reprogramming to support their activation, differentiation, and ultimately function. In the spirit of Sir Archibald Garrod, this metabolic reprogramming actually imparts a chemical individuality which confers advantage, while in others confers vulnerability, depending upon the milieu. Studying T cell immunometabolism in the context of inborn errors of metabolism allows one to define essential pathways of intermediary metabolism as well metabolic vulnerabilities and plasticity. Inborn errors of metabolism, a class of diseases first named by Garrod, have a long history of being informative for common physiologic and pathologic processes. This endeavor may be accomplished through the study of patients, animal models, and in vitro models of inborn errors of metabolism. In this review, the basics of intermediary metabolism and core metabolic pathways will be discussed, along with their relationship to T cell immunometabolism.Due to their pleiotropic nature, the reader will be specifically directed toward various inborn errors of metabolism which may be helpful for answering important questions about the role of metabolism in T cells. K E Y W O R D Simmunometabolism, inborn errors of metabolism, T cells

Immunometabolism: From basic mechanisms to translation

“…In particular, Mendelian genetic metabolic disorders provide insight into genes and pathways essential for normal metabolic function and influence on immunity, as reviewed in detail by McGuire. 59 While the majority of these diverse disorders have not presented apparent immunological phenotypes, immune cells have not yet been extensively explored in these settings. With clear examples, such as glycogen storage disease-1b that leads to lymphopenia and diminished ability of T cells to upregulate glycolysis, it is apparent that these human genetic diseases can provide a wide-ranging opportunity for immunometabolic discovery.…”

“…One approach to identify novel immunometabolic regulators is to take a human genetics strategy. In particular, Mendelian genetic metabolic disorders provide insight into genes and pathways essential for normal metabolic function and influence on immunity, as reviewed in detail by McGuire 59 . While the majority of these diverse disorders have not presented apparent immunological phenotypes, immune cells have not yet been extensively explored in these settings.…”

The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective

“…Despite the great diversity in the clinical presentations and management strategies of different IEM, they mostly share in common their need for challenging diagnostic procedures requiring specialized labs and for multidisciplinary collaborative medical teams for acute and long-term treatment and patient monitoring. Children and adults with an IEM are particularly at higher risk of morbidity and mortality when infected with SARS-CoV-2 due to their chronic preexisting conditions and potentially vulnerable immune system [ 4 , 5 ]. Furthermore, due to the pandemic itself or due to the forced reorganization of health care system activities needed to face the pandemic in many countries [ 6 ], medical services dedicated to IEM patients have also been impacted.…”

Friend or foe of innate lymphoid cells in inflammation‐associated cardiovascular disease

“…The pathological lesion in the arterial intima continuously accumulates and increases the size of the intima under the influence of inflammatory factors, forming an inflammatory structure called plaque where contains a lot of inflammatory cells. In human plaques, T cells account for about 10%, of which 70% are regarded as CD4 + T cells, and the others largely CD8 + T cells 72 . Most CD4 + T cells in the vessel wall are Th1 cells, which promote the development of atherosclerosis by producing TNF‐α and IFN‐γ.…”