日本研究人員日前發(fā)表研究報告說,，細胞內的芳香烴受體蛋白（Ahr蛋白）對類風濕關節(jié)炎形成發(fā)揮了關鍵作用,。這一發(fā)現(xiàn)將有助于開發(fā)治療類風濕性關節(jié)炎的新藥物,。
類風濕性關節(jié)炎是手腳等關節(jié)部位的慢性炎癥,，往往會導致關節(jié)和周邊骨骼功能破壞和畸形,。此前的研究已發(fā)現(xiàn),，人體免疫機能過度發(fā)揮作用是導致類風濕性關節(jié)炎的病因,，一種稱為“Th17細胞”的淋巴細胞會生成過量的促炎癥因子,，使關節(jié)部位炎癥持久不退。
日本大阪大學等機構研究人員組成的聯(lián)合研究小組,，對患有膠原性類風濕關節(jié)炎的實驗鼠進行了分析,。他們發(fā)現(xiàn)，如果抑制免疫T細胞群的芳香烴受體蛋白,，實驗鼠體內的“Th17”細胞就會減少,，類風濕性關節(jié)炎癥狀就減輕。如果在另一種免疫細胞——巨噬細胞中抑制芳香烴受體蛋白,，則無此效果,。
芳香烴受體蛋白是哺乳動物和爬行動物體內廣泛存在的一種蛋白質，其具體功能目前還不清楚,。研究小組認為,，人體免疫系統(tǒng)發(fā)出錯誤指令,，導致免疫T細胞群中芳香烴受體蛋白過量，“Th17”細胞異常增加,，最終引發(fā)了類風濕性關節(jié)炎,。
研究小組成員、大阪大學教授岸本忠三說,，如果能開發(fā)遏制芳香烴受體蛋白功能的藥物,，也許能夠治療類風濕性關節(jié)炎。
日本研究人員的成果刊登在新一期美國《國家科學院院刊》上,。(生物谷 Bioon.com)
doi: 10.1073/pnas.1111786108
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Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis
Nakahama, Taisuke; Kimura, Akihiro; Nguyen, Nam Trung; Chinen, Ichino; Hanieh, Hamza; Nohara, Keiko; Fujii-Kuriyama, Yoshiaki; Kishimoto, Tadamitsu
The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis have not been elucidated.Here, we show that Ahr deficiency ameliorated collagen-induced arthritis, a mouse model of RA. Collagen-immunized Ahr KO miceshowed decreased serum levels of such proinflammatory cytokines as IL-1β and IL-6. The Th17 and Th1 cell populations in lymphnodes from these mice decreased and increased, respectively, whereas the percentage of regulatory T cells was unchanged. Interestingly,a lack of Ahr specifically in T cells significantly suppressed collagen-induced arthritis development, whereas Ahr deficiencyin macrophages had no effect. These finding indicate that the development of experimental autoimmune arthritis depends onthe presence of Ahr in T cells, and that Th1/Th17 balance may be particularly important for this process.
