title: 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.affiliation: Shanghai Key Laboratory of Signalling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D000818:Animals; D019390:Arrestins / Q000172:deficiency* / Q000235:genetics; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605255:Arrb1 protein, mouse; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D049452:Green Fluorescent Proteins
keywords: experimental autoimmune encephalomyelitis; regulatory T cells; β-arrestin 2