ババ　ノブヤス   馬場　伸育    所属   川崎医科大学  医学部 基礎医学　免疫学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The aryl hydrocarbon receptor (AhR) ligand VAF347 selectively acts on monocytes and naïve CD4(+) Th cells to promote the development of IL-22-secreting Th cells.
掲載誌名	正式名：Human immunology 略　 称：Hum Immunol ISSNコード：18791166/01988859
掲載区分	国外
巻・号・頁	73(8),pp.795-800
著者・共著者	Nobuyasu Baba, Manuel Rubio, Linda Kenins, Camille Regairaz, Maximilian Woisetschlager, José M Carballido, Marika Sarfati
発行年月	2012/08
概要	The low molecular weight compound VAF347, and its pro-drug version VAG539, interact with the transcription factor aryl hydrocarbon receptor (AhR) on monocytes to mediate its anti-inflammatory activity in vitro and in vivo. AhR is a crucial factor for IL-22 production, which regulates skin and gut homeostasis. Here we investigated whether VAF347 might control the differentiation of naïve T cells into IL-22-secreting cells and/or regulate IL-22 production by memory T cells. Human monocytes exposed to VAF347 differentiated into dendritic cells capable of instructing a naïve CD4(+) T cell differentiation program that promoted IL-22 secretion and concomitantly inhibited IL-17 production. Whilst AhR ligation by VAF347 on naïve CD4(+) T cells favored the development of single IL-22-secreting cells (Th22), it suppressed the generation of T cells secreting either IL-22 and IFN-γ or IL-17 and IFN-γ. In contrast, memory T cells were refractory to AhR regulation since VAF347, AhR antagonist or AhR gene silencing did not modulate the production of any of these cytokines. Interfering with AhR functions using VAF347 may provide an efficient way to intervene with autoimmune disease since it would enhance the host protective function mediated by IL-22 while preventing the development of Th cells secreting pro-inflammatory cytokines.
DOI	10.1016/j.humimm.2012.05.002
PMID	22609446