Metabolic Impairment of Natural Killer Cells in Type 2 Diabetes (T2D) Individuals: A Double-Edged Sword Elevating Susceptibility to Infections and Cancer

Abstract

ABSTRACT: Glucose metabolism disturbances, such as the intricate realm of type 2 diabetes mellitus (T2DM), cast a captivating spell on the biological landscape of natural killer cells (NK cells). However, the scientific tapestry depicting the abundance and functionality of NK cells in T2DM remains an enigma, with studies yielding inconsistent findings. Some reports have unveiled a decline in peripheral NK cell numbers among T2DM patients compared to their healthy counterparts 1, while others have painted a different picture, suggesting similar levels of NK cells between T2DM patients and controls 2. Intriguingly, patients with diabetes showcased diminished NK cell activity when pitted against control participants 3. Nonetheless, a contrasting study revealed comparable levels of NK cells and their functional prowess between T2DM individuals and the control group 4. In the realm of inflammation, a symphony of cytokines, including the illustrious interleukin 18 (IL-18), takes center stage, orchestrating the proliferation and effector functions of NK cells. Astonishingly, patients afflicted by T2DM exhibit elevated IL-18 levels 5. In a prior investigation of my own, I unraveled the fascinating connection between IL-18 and NK cell biology. It became evident that IL-18 enhances the expression of nutrient transporters on NK cells, thereby bolstering their metabolic fitness an essential prerequisite for cellular division and the execution of their formidable effector functions 6. Hence, these intriguing findings hint at a possible link between the metabolic landscape of NK cells and their response to IL-18, potentially elucidating the discordant outcomes observed in NK cell functionality during the course of T2DM. Diving deeper into the realm of immune cell metabolism holds tremendous promise for therapeutic breakthroughs in the realm of chronic diseases. Recent studies have illuminated the intricate interplay between compromised immune responses and defective cellular metabolism, underscoring the urgent need to unravel the intricate dance between these two realms in the context of chronic diseases.