دورية أكاديمية
Lead suppresses interferon γ to induce splenomegaly via modification on splenic endothelial cells and lymphoid tissue organizer cells in mice
| العنوان: | Lead suppresses interferon γ to induce splenomegaly via modification on splenic endothelial cells and lymphoid tissue organizer cells in mice |
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| المؤلفون: | Yue Zhai, Yifan Zhao, Yufan Zhang, Jinyi He, Mengke Tang, Yalin Liu, Guangrui Yang, Peng Xue, Ye Yao, Miao He, Yanyi Xu, Weidong Qu, Yubin Zhang |
| المصدر: | Ecotoxicology and Environmental Safety, Vol 244, Iss , Pp 114046- (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Environmental pollution LCC:Environmental sciences |
| مصطلحات موضوعية: | Lead, Splenomegaly, Endothelial cells, Lymphoid tissue organizer cells, Interferon γ/Jak1/STAT1, NF-κB, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
| الوصف: | Splenomegaly is a symptom characterized by the presence of an enlarged spleen. The impact of environmental factors on splenomegaly is largely unknown. In this study, C57BL/6 mice were treated with 125 ppm or 1250 ppm lead (Pb) via drinking water for 8 wk, and the process of splenomegaly was evaluated. Treatment with 1250 ppm Pb, but not 125 ppm Pb, caused splenomegaly, which was associated with increased capacity for erythrocyte clearance. Intriguingly, Pb-caused splenomegaly was independent of lymphoid tissue inducer (LTi) cells, which produce lymphotoxins α and β (LTα/β) to activate endothelial cells and LT organizer (LTo) cells and drive the development of spleen physiologically. A direct action of Pb on endothelial cells and LTo cells did not impact their proliferation. On the other hand, during steady state, a tonic level of interferon (IFN)γ acted on endothelial cells and LTo cells to suppress splenomegaly, as IFNγ receptor (IFNγR)-deficient mice had enlarged spleens relative to wild-type mice; during Pb exposure, splenic IFNγ production was suppressed, thus leading to a loss of the inhibitory effect of IFNγ on splenomegaly. Mechanically, Pb acted on splenic CD4+ T cells to suppress IFNγ production, which impaired the Janus kinase (Jak)1/ signal transducer and activator of transcription (STAT)1 signaling in endothelial cells and LTo cells; the weakened Jak1/STAT1 signaling resulted in the enhanced nuclear factor-κB (NF-κB) signaling in endothelial cells and LTo cells, which drove their proliferation and caused splenomegaly. The present study reveals a previously unrecognized mechanism for the immunotoxicity of Pb, which may extend our current understanding for Pb toxicology. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0147-6513 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S0147651322008867Test; https://doaj.org/toc/0147-6513Test |
| DOI: | 10.1016/j.ecoenv.2022.114046 |
| الوصول الحر: | https://doaj.org/article/5e928b229f1348298f106f189523aa83Test |
| رقم الانضمام: | edsdoj.5e928b229f1348298f106f189523aa83 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 01476513 |
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| DOI: | 10.1016/j.ecoenv.2022.114046 |