The international journal of biochemistry & cell biology · 2026
LCN2 modulates Th17/Treg balance in vitro and is associated with an adaptive response to intestinal ischemia-reperfusion injury under Hmox1-deficient conditions.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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.
Chen Wendong, Li Junjie, Shao Jianlin, Yang Meixu, Tan Ying, Yang Wei
Аннотация
INTRODUCTION: Intestinal ischemia-reperfusion (I/R) injury is a critical clinical condition involving oxidative stress, inflammation, and immune dysregulation, often leading to significant morbidity and mortality. This study investigates the protective mechanisms of Heme oxygenase-1 (Hmox1) against I/R-induced intestinal damage, focusing on its regulation of Th17/Treg cell balance via Lipocalin 2 (LCN2).
MATERIAL AND METHODS: Male wild-type mice and Hmox1-deficient mice were used to induce an intestinal I/R injury model. Histological analysis, ELISA, immunohistochemistry, immunofluorescence, flow cytometry, RT-qPCR, Western blotting, and RNA sequencing were used to evaluate intestinal injury, cytokine levels, and immune cell profiles. Transcriptomic analysis was conducted to identify differentially expressed genes and pathways involved in the immune response. Naive CD4 + T cells were isolated for in vitro differentiation experiments to analyze the role of LCN2 in Th17 and Treg differentiation under Hmox1-deficient conditions.
RESULTS: Hmox1 deficiency was associated with more severe intestinal mucosal injury, higher IL-6 and TNFα levels, enhanced Th17-associated responses, and reduced Treg-associated signals after I/R. Transcriptomic analysis indicated enrichment of IL-17, JAK-STAT, and TNFα signaling pathways. LCN2 expression increased after I/R and was further elevated in Hmox1-deficient I/R samples. In vitro, LCN2 knockdown enhanced Th17 polarization and further reduced Treg differentiation under oxidative/inflammatory stimulation, suggesting that LCN2 may participate in a compensatory immune-regulatory response.
CONCLUSION: These findings underline the crucial role of Hmox1 in preserving intestinal immune homeostasis during I/R injury and identify LCN2 as a candidate compensatory regulator of Th17/Treg balance under Hmox1-deficient conditions. LCN2 may therefore represent a potential target for non-Hmox1-dependent strategies to ameliorate intestinal I/R injury.
MATERIAL AND METHODS: Male wild-type mice and Hmox1-deficient mice were used to induce an intestinal I/R injury model. Histological analysis, ELISA, immunohistochemistry, immunofluorescence, flow cytometry, RT-qPCR, Western blotting, and RNA sequencing were used to evaluate intestinal injury, cytokine levels, and immune cell profiles. Transcriptomic analysis was conducted to identify differentially expressed genes and pathways involved in the immune response. Naive CD4 + T cells were isolated for in vitro differentiation experiments to analyze the role of LCN2 in Th17 and Treg differentiation under Hmox1-deficient conditions.
RESULTS: Hmox1 deficiency was associated with more severe intestinal mucosal injury, higher IL-6 and TNFα levels, enhanced Th17-associated responses, and reduced Treg-associated signals after I/R. Transcriptomic analysis indicated enrichment of IL-17, JAK-STAT, and TNFα signaling pathways. LCN2 expression increased after I/R and was further elevated in Hmox1-deficient I/R samples. In vitro, LCN2 knockdown enhanced Th17 polarization and further reduced Treg differentiation under oxidative/inflammatory stimulation, suggesting that LCN2 may participate in a compensatory immune-regulatory response.
CONCLUSION: These findings underline the crucial role of Hmox1 in preserving intestinal immune homeostasis during I/R injury and identify LCN2 as a candidate compensatory regulator of Th17/Treg balance under Hmox1-deficient conditions. LCN2 may therefore represent a potential target for non-Hmox1-dependent strategies to ameliorate intestinal I/R injury.