Related Experiment Video

Updated: Sep 13, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.2K

Lithium suppresses the Ras-Raf-MEK-ERK signaling in CD4 T cells and impairs the humoral immune system

Jiaojiao Wu1, Yifan Zhao1, Jie Zhang1

  • 1Experimental Center for Research, School of Public Health and Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|July 25, 2025
PubMed

Lithium (Li) is a metal that broadly exists in human bodies. To date, the impact of Li on the humoral immune system remains to be defined. In this study, C57BL/6 mice treated with 50 or 200 ppm Li for 3 months and human peripheral blood mononuclear cells (PBMC) treated with Li in vitro were used. Treatment with 200 ppm Li suppressed the production of serum IgG, but not serum IgM in mice; treatment with 200 ppm Li impaired the activation of CD4 T cells and B cells, and the production of germinal center in mice. Mechanistically, treatment with 200 ppm Li impaired the Ras-Raf-MEK-ERK signaling in CD4 T cells and thereby suppressed the humoral immune system in mice. In line with this, in vitro treatment with Li on human PBMC decreased the production of IgG, but not IgM in the supernatants; in vitro treatment with Li on human PBMC suppressed the activation of CD4 T cells and impaired the Ras-Raf-MEK-ERK signaling in CD4 T cells. Collectively, the present study indicated that Li impaired the humoral immune system via repressing the Ras-Raf-MEK-ERK signaling in CD4 T cells, which was a previously unrecognized immunotoxicity of Li.

Keywords:
CD4 T cellsLithiumThe Ras-Raf-MEK-ERK signalingThe humoral immune system

More Related Videos

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice07:17

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

Published on: June 22, 2016

10.0K
Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance14:01

Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance

Published on: July 22, 2011

14.7K

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
Immunodeficiency Diseases01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
1.2K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.1K
Pulmonary Tuberculosis I01:29

Pulmonary Tuberculosis I

Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
326
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.4K