1.UCSF, 513 Parnassus Ave., S-1004, San Francisco, CA 94143, USA.
J Leukoc Biol. 2013 Nov;94(5):877-84. doi: 10.1189/jlb.0213084. Epub 2013 Aug 7.
Arg1 is produced by AAMs and is proposed to have a regulatory role during asthma and allergic inflammation. Here, we use an Arg1 reporter mouse to identify additional cellular sources of the enzyme in the lung. We demonstrate that ILC2s express Arg1 at rest and during infection with the migratory helminth Nippostrongylus brasiliensis. In contrast to AAMs, which express Arg1 following IL-4/IL-13-mediated STAT6 activation, ILC2s constitutively express the enzyme in a STAT6-independent manner. Although ILC2s deficient in the IL-33R subunit T1/ST2 maintain Arg1 expression, IL-33 can regulate total lung Arg1 by expanding the ILC2 population and by activating macrophages indirectly via STAT6. Finally, we find that ILC2 Arg1 does not mediate ILC2 accumulation, ILC2 production of IL-5 and IL-13, or collagen production during N. brasiliensis infection. Thus, ILC2s are a novel source of Arg1 in resting tissue and during allergic inflammation.
Arg1 由 AAMs 产生,据推测在哮喘和过敏炎症中具有调节作用。在这里,我们使用 Arg1 报告小鼠来鉴定肺中该酶的其他细胞来源。我们证明,ILC2 在静止期和感染迁徙性蠕虫旋毛虫时表达 Arg1。与 AAMs 不同,AAMs 在 IL-4/IL-13 介导的 STAT6 激活后表达 Arg1,ILC2 以 STAT6 非依赖性方式组成性表达该酶。尽管缺乏 IL-33R 亚基 T1/ST2 的 ILC2 仍然表达 Arg1,但 IL-33 可以通过扩展 ILC2 群体并通过 STAT6 间接激活巨噬细胞来调节总肺 Arg1。最后,我们发现 ILC2 Arg1 不介导 N. brasiliensis 感染期间 ILC2 的积累、ILC2 产生 IL-5 和 IL-13 或胶原的产生。因此,ILC2 是静止组织和过敏炎症期间 Arg1 的新来源。