CD4(+)Foxp3(+) Tregs protect against innate immune cell-mediated fulminant hepatitis in mice.

Abstract

UNLABELLED:

Foxp3(+) Tregs play important roles in maintaining homeostasis by suppressing excessive immune responses that result in serious tissue damage; yet, it is largely unknown about the impact of Tregs on innate immune cells in hepatitis models in vivo. In this study, we examined the effect of hepatic Tregs on innate immune-mediated liver injury by using the murine model of polyI:C and d-galactosamine (d-GalN)-induced hepatitis. Administration of polyI:C/d-GalN increased the number of CD4(+)Foxp3(+) Tregs in the liver. Depletion of Tregs leaded to higher levels of proinflammatory cytokine expression and severer liver injury, whereas adoptive transfer of Foxp3(+) Tregs attenuated liver injury in polyI:C/d-GalN-treated mice. In addition, depletion of Tregs leaded to a reduction in TGF-β and IL-10 expression in polyI:C/d-GalN-treated mice. Both of these cytokines were important for suppression of polyI:C/d-GalN-induced liver injury. TGF-β was derived from Tregs. IL-10 was derived from active Kupffer cells, and coincubation of Kupffer cells with Tregs increased IL-10 secretion. Furthermore, TGF-β blockade abrogated Treg-mediated suppression of proinflammatory cytokine production by innate immune cell in vitro.

CONCLUSION:

CD4(+)Foxp3(+) Tregs modify innate immune responses in polyI:C/d-GalN-induced fulminant hepatitis via producing TGF-β and enhancing IL-10 secretion by Kupffer cells.

• Authors: Xin Hou, Jing Song, Jun Su, Dake Huang, Wenda Gao, Jun Yan, Jijia Shen
• Journal: Molecular immunology (Mol Immunol) Vol. 63 Issue 2 Pg. 420-7 (Feb 2015) ISSN: 1872-9142 [Electronic] England
• PMID: 25315497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• CD4 Antigens
• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukin-2 Receptor alpha Subunit
• Protective Agents
• Galactosamine
• Poly I-C

Topics

• Adoptive Transfer
• Animals
• CD4 Antigens (metabolism)
• Cytokines (metabolism)
• Forkhead Transcription Factors (metabolism)
• Galactosamine (administration & dosage)
• Hepatitis (immunology, pathology, prevention & control)
• Immunity, Innate (drug effects)
• Injections
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Kupffer Cells (drug effects, metabolism)
• Liver (drug effects, immunology, pathology)
• Lymphocyte Depletion
• Male
• Mice, Inbred C57BL
• Poly I-C (administration & dosage, pharmacology)
• Protective Agents (metabolism)
• T-Lymphocytes, Regulatory (immunology)