Th17 Cells, Glucocorticoid Resistance, and Depression

Abstract

Depression is a severe mental disorder that disrupts mood and social behavior and is one of the most common neuropsychological symptoms of other somatic diseases. During the study of the disease, a number of theories were put forward (monoamine, inflammatory, vascular theories, etc.), but none of those theories fully explain the pathogenesis of the disease. Steroid resistance is a characteristic feature of depression and can affect not only brain cells but also immune cells. T-helper cells 17 type (Th17) are known for their resistance to the inhibitory effects of glucocorticoids. Unlike the inhibitory effect on other subpopulations of T-helper cells, glucocorticoids can enhance the differentiation of Th17 lymphocytes, their migration to the inflammation, and the production of IL-17A, IL-21, and IL-23 in GC-resistant disease. According to the latest data, in depression, especially the treatment-resistant type, the number of Th17 cells in the blood and the production of IL-17A is increased, which correlates with the severity of the disease. However, there is still a significant gap in knowledge regarding the exact mechanisms by which Th17 cells can influence neuroinflammation in depression. In this review, we discuss the mutual effect of glucocorticoid resistance and Th17 lymphocytes on the pathogenesis of depression.

“Air That Once Was Breath” Part 1: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation – “Climate Change, Allergy and Immunology” Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023

“…While glucocorticoid responsiveness varies among individuals depending on genetic, environmental, and immune factors, wildfire-smoke-induced oxidative stress, inflammatory mediators, and epigenetic changes [61,104,134,135] can all reduce immune cell glucocorticoid responsiveness leading to persistent inflammation. IL-17 is particularly interesting in this mechanism for several reasons [136].…”

“Air That Once Was Breath” Part 2: Wildfire Smoke and Airway Disease – “Climate Change, Allergy and Immunology” Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023

“…IL-17A is implicated in wildfire smoke-induced airway inflammation [61] and plays a central role in the immune response [62]. It directly activates signaling pathways like NF-κB, p38-MAPK, and PI3K, which antagonize glucocorticoid receptor function, further contributing to glucocorticoid resistance [58,63]. Better understanding the potential central role of IL-17A in the interplay between wildfire smoke exposure, psychosocial stress, and glucocorticoid resistance is necessary to tailor treatment strategies for affected individuals.…”