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Lead suppresses interferon γ to induce splenomegaly via modification on splenic endothelial cells and lymphoid tissue organizer cells in mice.
- Source :
- Ecotoxicology & Environmental Safety; Oct2022, Vol. 244, pN.PAG-N.PAG, 1p
- Publication Year :
- 2022
-
Abstract
- 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<superscript>+</superscript> 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. [Display omitted] • Lead suppresses the production of IFNγ from CD4 T cells in the spleen. • The decreased IFNγ impairs the Jak1/STAT1 signaling in endothelial and LTo cells. • The weakened Jak1/STAT1 signaling activates the NF-κB signaling. • The enhanced NF-κB signaling in endothelial and LTo cells drives splenomegaly. [ABSTRACT FROM AUTHOR]
- Subjects :
- LYMPHOID tissue
LEAD
LEAD exposure
INTERFERONS
DIRECT action
INTERFERON receptors
Subjects
Details
- Language :
- English
- ISSN :
- 01476513
- Volume :
- 244
- Database :
- Supplemental Index
- Journal :
- Ecotoxicology & Environmental Safety
- Publication Type :
- Academic Journal
- Accession number :
- 159216467
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2022.114046