Xu Hui, Oriss Timothy B, Fei Mingjian, Henry Adam C, Melgert Barbro N, Chen Li, Mellor Andrew L, Munn David H, Irvin Charles G, Ray Prabir, Ray Anuradha
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine and Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Proc Natl Acad Sci U S A. 2008 May 6;105(18):6690-5. doi: 10.1073/pnas.0708809105. Epub 2008 Apr 24.
Indoleamine 2,3 dioxygenase (IDO) has emerged as an important mediator of immune tolerance via inhibition of Th1 responses. However, the role of IDO in antigen-induced tolerance or allergic inflammation in the airways that is regulated by Th2 responses has not been elucidated. By using IDO(-/-) mice, we found no impairment of airway tolerance, but, surprisingly, absence of IDO provided significant relief from establishment of allergic airways disease, as evident from attenuated Th2 cytokine production, airway inflammation, mucus secretion, airway hyperresponsiveness, and serum ovalbumin-specific IgE. Myeloid dendritic cells isolated from lung-draining lymph nodes of mice immunized for either Th1 or Th2 response revealed fewer mature dendritic cells in the lymph nodes of IDO(-/-) mice. However, the net functional impact of IDO deficiency on antigen-induced responses was more remarkable in the Th2 model than in the Th1 model. Collectively, these data suggest that IDO is not required for the induction of immune tolerance in the airways but plays a role in promoting Th2-mediated allergic airway inflammation via unique effects on lung dendritic cells.
吲哚胺2,3-双加氧酶（IDO）已成为通过抑制Th1反应介导免疫耐受的重要介质。然而，IDO在由Th2反应调节的抗原诱导的耐受或气道过敏性炎症中的作用尚未阐明。通过使用IDO基因敲除小鼠，我们发现气道耐受性未受损，但令人惊讶的是，IDO的缺失显著减轻了过敏性气道疾病的发生，这从Th2细胞因子产生减少、气道炎症、黏液分泌、气道高反应性以及血清卵清蛋白特异性IgE水平降低可以明显看出。从小鼠肺引流淋巴结中分离出的髓样树突状细胞，无论是针对Th1反应还是Th2反应进行免疫，在IDO基因敲除小鼠的淋巴结中成熟树突状细胞数量均较少。然而，IDO缺乏对抗原诱导反应的净功能影响在Th2模型中比在Th1模型中更为显著。总体而言，这些数据表明，IDO并非气道免疫耐受诱导所必需，但通过对肺树突状细胞的独特作用，在促进Th2介导的过敏性气道炎症中发挥作用。
