Strober Warren, Kitani Atsushi, Fichtner-Feigl Stefan, Fuss Ivan J
Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Mol Med. 2009 Aug;9(6):740-50. doi: 10.2174/156652409788970652.
The IL-13Ralpha2 receptor is a high affinity receptor for IL-13 that is used only by IL-13 and is quite distinct from the well known IL-13Ralpha1 receptor that IL-13 shares with IL-4. It was widely considered to be a secreted receptor that is devoid of signaling activity and functional only as a decoy receptor that retarded signaling via IL-13Ralpha1. In recent studies, however, it was shown to be capable of robust signaling that results in production of TGF-beta1 and through the latter cytokine, the induction of fibrosis occuring in various experimental inflammatory states. Thus, in initial studies, IL-13 signaling via IL-13Ralpha2 was shown to play an important role in the fibrosis developing in both oxazolone colitis and bleomycin-induced pulmonary fibrosis; later, it was also shown to be critical to the development of fibrosis in a model of chronic colitis induced by trinitrobenzene sulphonic acid (TNBS). These studies suggest that blockade of IL-13 or IL-13Ralpha2 signaling might be an excellent target for the prevention of inflammation-associated fibrosis. A second role of IL-13 signaling via IL-13Ralpha2 is in tumor immune surveillance. Thus, in the relevant studies it was shown that NKT cells stimulated by tumor antigens produce IL-13 that then acts on Gr-1 cells to induce TGF-beta1; the latter then inhibits CD8+ T cells engaged in tumor immune surveillance; in effect, then, receptor signaling favors tumor growth. In addition to its signaling function and the induction of TGF-beta1, IL-13Ralpha2 also influences IL-13Ralpha1 signaling in complex ways; thus, IL-13Ralpha2 emerges as a important component of IL-13 signaling, not only in its own right but also in its possible effect on its companion receptor.
白细胞介素-13α2受体（IL-13Rα2）是白细胞介素-13（IL-13）的高亲和力受体，仅被IL-13所利用，与IL-13和白细胞介素-4（IL-4）共同使用的著名的白细胞介素-13α1受体截然不同。它曾被广泛认为是一种分泌型受体，缺乏信号传导活性，仅作为一种诱饵受体发挥作用，通过阻碍白细胞介素-13α1介导的信号传导来发挥功能。然而，最近的研究表明，它能够进行强大的信号传导，导致转化生长因子-β1（TGF-β1）的产生，并通过后者这种细胞因子，在各种实验性炎症状态下诱导纤维化的发生。因此，在最初的研究中，经由IL-13Rα2的IL-13信号传导被证明在恶唑酮结肠炎和博来霉素诱导的肺纤维化中发生的纤维化过程中发挥重要作用；后来，在三硝基苯磺酸（TNBS）诱导的慢性结肠炎模型中，它也被证明对纤维化的发展至关重要。这些研究表明，阻断IL-13或IL-13Rα2信号传导可能是预防炎症相关纤维化的一个极佳靶点。经由IL-13Rα2的IL-13信号传导的第二个作用是在肿瘤免疫监视方面。因此，在相关研究中表明，肿瘤抗原刺激的自然杀伤T细胞（NKT细胞）产生IL-13，然后IL-13作用于粒细胞集落刺激因子-1（Gr-1）细胞以诱导TGF-β1；后者随后抑制参与肿瘤免疫监视的CD8 + T细胞；实际上，受体信号传导有利于肿瘤生长。除了其信号传导功能和对TGF-β1的诱导作用外，IL-13Rα2还以复杂的方式影响IL-13Rα1信号传导；因此，IL-13Rα2不仅本身，而且其对伴侣受体可能产生的影响，都成为IL-13信号传导的一个重要组成部分。
