Allakhverdi Zoulfia, Smith Dirk E, Comeau Michael R, Delespesse Guy
Laboratory on Allergy, Centre Hospitalier de l'Université de Montréal Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.
J Immunol. 2007 Aug 15;179(4):2051-4. doi: 10.4049/jimmunol.179.4.2051.
IL-33, the natural ligand of the IL-1 receptor family member ST2L, is known to enhance experimental allergic-type inflammatory responses by costimulating the production of cytokines from activated Th2 lymphocytes. Although ST2L has long been known to be expressed by mast cells, its role in their biology has not been explored. In this study we report that IL-33 directly stimulates primary human mast cells (MCs) to produce several proinflammatory cytokines and chemokines and also exerts a permissive effect on the MCs response to thymic stromal lymphopoietin, a recently described potent MCs activator. IL-33 also acts both alone and in concert with thymic stromal lymphopoietin to accelerate the in vitro maturation of CD34(+) MC precursors and induce the secretion of Th2 cytokines and Th2-attracting chemokines. Taken together, these results suggest that IL-33 may play an important role in mast cell-mediated inflammation and further emphasize the role of innate immunity in allergic diseases.
白细胞介素-33（IL-33）是白细胞介素-1受体家族成员ST2L的天然配体，已知它通过共刺激活化的Th2淋巴细胞产生细胞因子来增强实验性过敏型炎症反应。尽管早就知道ST2L由肥大细胞表达，但其在肥大细胞生物学中的作用尚未得到探索。在本研究中，我们报告IL-33直接刺激原代人肥大细胞（MCs）产生多种促炎细胞因子和趋化因子，并且对MCs对胸腺基质淋巴细胞生成素（一种最近描述的强效MCs激活剂）的反应发挥允许作用。IL-33还单独或与胸腺基质淋巴细胞生成素协同作用，加速CD34(+) MC前体细胞的体外成熟，并诱导Th2细胞因子和吸引Th2的趋化因子的分泌。综上所述，这些结果表明IL-33可能在肥大细胞介导的炎症中起重要作用，并进一步强调了固有免疫在过敏性疾病中的作用。
