Loss of β-arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells.

Abstract

β-Arrestins are well-known regulators and mediators of G protein-coupled receptor signalling, and accumulating evidence reveals that they are functionally involved in inflammation and autoimmune diseases. Of the two β-arrestins, β-arrestin 1 is documented to play regulatory roles in an animal model of multiple sclerosis (MS), whereas the role of β-arrestin 2 is less clear. Here, we show that β-arrestin 2-deficient mice displayed the exacerbated and sustained symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. At the cellular level, deficiency of β-arrestin 2 led to a decreased number of Foxp3(+) CD4(+) regulatory T (Treg) cells in peripheral lymphoid organs of EAE mice. Consistently, our in vitro observations also revealed that loss of β-arrestin 2 impaired the conversion of Foxp3(-) CD4(+) T cells into Foxp3(+) CD4(+) inducible Treg cells. Taken together, our data suggest that β-arrestin 2 plays a regulatory role in MS, that is opposite to that of β-arrestin 1, in autoimmune diseases such as MS, which is at least partially through regulation of iTreg cell differentiation.

• Authors: Yu Zhang, Chang Liu, Bin Wei, Gang Pei
• Journal: Immunology (Immunology) Vol. 140 Issue 4 Pg. 430-40 (Dec 2013) ISSN: 1365-2567 [Electronic] England
• PMID: 23859136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• Arrb1 protein, mouse
• Arrb2 protein, mouse
• Arrestins
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• beta-Arrestin 1
• beta-Arrestin 2
• beta-Arrestins
• Green Fluorescent Proteins

Topics

• Animals
• Arrestins (deficiency, genetics)
• CD4 Lymphocyte Count
• Cell Differentiation
• Central Nervous System (immunology, metabolism)
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, metabolism)
• Forkhead Transcription Factors (genetics, metabolism)
• Genes, Reporter
• Green Fluorescent Proteins (genetics, metabolism)
• Lymphoid Tissue (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Signal Transduction
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Time Factors
• beta-Arrestin 1
• beta-Arrestin 2
• beta-Arrestins