Frontiers in immunology · 2026
Glycine receptors in circulating white blood cells regulated by neuroinflammation.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Thakur Vikram, Chokpapone Yathip Mindy, Mishra Rakshak, Evbuomwan Osarenoma, Lopez Lizbeth, Guerrero Camila, Chavez Alexandra, Carrizales Ingrid, Rodriguez Brianna J, Lavezo Jonathan, Rodriguez Gustavo J, Dou Huanyu
Аннотация
INTRODUCTION: Neuroinflammation is involved in a wide range of neurological disorders, yet the lack of minimally invasive biomarkers hampers early diagnosis and therapeutic monitoring. Glycine receptors (GlyRs), classically known as inhibitory neurotransmitter receptors in the central nervous system, are increasingly recognized as regulators of immune signaling. Here, we identify GlyRs as novel peripheral indicators of neuroinflammation.
METHODS AND RESULTS: We demonstrate that GlyRα1, α2, and α3 subunits are constitutively expressed in human and murine immune cells, with GlyRα2 predominating across peripheral tissues and the brain. Using ex vivo and in vivo mouse models, we found that the expression of GlyRα1, α2, and α3 in macrophages and circulating white blood cells (WBCs) was not directly mediated by inflammatory cytokine signaling in the brain or WBCs. Neuroinflammation upregulates GlyRα1 and α3 expression in the brain, spleen, bone marrow, and circulating WBCs. Immunostaining revealed GlyRα3 to the membrane and GlyRα1/2 to both the membrane and cytoplasm of WBCs. GlyR expression was also observed in the bone marrow, the spleen (macrophage-rich red pulp), and the neurons. Notably, GlyRα1 and α3 expression in WBCs was significantly elevated in neuroinflammation compared to control and systemic inflammation models. Changes in GlyR expression were not correlated with the expression of pro-inflammatory cytokines in the brain and WBCs. LPS-induced microglial (Iba1+) activation paralleled the upregulation of WBC GlyR, suggesting a reciprocal modulation between central and peripheral compartments.
CONCLUSION: Together, these findings define a brain-glycinergic signaling-blood axis that maintains homeostatic protectivity. GlyR subunits, particularly GlyRα1 and α3, represent a neuropathology-induced modulation of GlyR signaling in peripheral immune cells.
METHODS AND RESULTS: We demonstrate that GlyRα1, α2, and α3 subunits are constitutively expressed in human and murine immune cells, with GlyRα2 predominating across peripheral tissues and the brain. Using ex vivo and in vivo mouse models, we found that the expression of GlyRα1, α2, and α3 in macrophages and circulating white blood cells (WBCs) was not directly mediated by inflammatory cytokine signaling in the brain or WBCs. Neuroinflammation upregulates GlyRα1 and α3 expression in the brain, spleen, bone marrow, and circulating WBCs. Immunostaining revealed GlyRα3 to the membrane and GlyRα1/2 to both the membrane and cytoplasm of WBCs. GlyR expression was also observed in the bone marrow, the spleen (macrophage-rich red pulp), and the neurons. Notably, GlyRα1 and α3 expression in WBCs was significantly elevated in neuroinflammation compared to control and systemic inflammation models. Changes in GlyR expression were not correlated with the expression of pro-inflammatory cytokines in the brain and WBCs. LPS-induced microglial (Iba1+) activation paralleled the upregulation of WBC GlyR, suggesting a reciprocal modulation between central and peripheral compartments.
CONCLUSION: Together, these findings define a brain-glycinergic signaling-blood axis that maintains homeostatic protectivity. GlyR subunits, particularly GlyRα1 and α3, represent a neuropathology-induced modulation of GlyR signaling in peripheral immune cells.