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CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice
Christophe Moreno1, Thierry Gustot, Charles Nicaise
1Division of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium. cmoreno@ulb.ac.be
Hepatology (Baltimore, Md.)
|September 22, 2005
Summary
Chemokine receptor CCR5 deficiency worsens T-cell-mediated hepatitis in mice. This exacerbates liver injury and immune cell infiltration, highlighting CCR5
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- T-cell-mediated hepatitis, induced by concanavalin A (Con A), involves cytokine/chemokine production and leukocyte infiltration.
- Chemokine receptor CCR5 and its ligands (CCL3, CCL4, CCL5) are crucial for leukocyte migration and activation.
Purpose of the Study:
- To investigate the role of the chemokine receptor CCR5 in concanavalin A (Con A)-induced liver injury.
Main Methods:
- Con A-induced hepatitis model in wild-type and CCR5-deficient (CCR5-/-) mice.
- Measurement of serum and hepatic chemokine ligand levels.
- Analysis of liver mononuclear cell infiltration and cytokine/chemokine production.
- In vivo neutralization of CCR5 ligands.
Main Results:
- CCR5-/- mice showed increased mortality and liver injury compared to wild-type mice after Con A administration.
- CCR5 deficiency led to elevated levels of interleukin 4, tumor necrosis factor alpha, CCL3, CCL4, and CCL5.
- A prominent liver mononuclear cell infiltrate, with many CCR1+ cells, was observed in CCR5-/- mice.
- Neutralization of CCL5 in CCR5-/- mice provided protection against hepatitis.
Conclusions:
- CCR5 deficiency exacerbates T-cell-mediated hepatitis, increasing liver injury and immune cell infiltration.
- CCR5 plays a protective role in immuno-mediated liver injury.
- Targeting CCL5 may offer therapeutic potential for managing T-cell-mediated hepatitis.